Incidental Mutation 'R1391:Brca1'
| ID |
162614 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Brca1
|
| Ensembl Gene |
ENSMUSG00000017146 |
| Gene Name |
breast cancer 1, early onset |
| Synonyms |
|
| MMRRC Submission |
039453-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1391 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
101488764-101551955 bp(-) (GRCm38) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 101526546 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Histidine to Leucine
at position 254
(H254L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000017290
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000017290]
[ENSMUST00000142086]
[ENSMUST00000191198]
|
| AlphaFold |
P48754 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000017290
AA Change: H254L
PolyPhen 2
Score 0.533 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000017290
Gene: ENSMUSG00000017146
AA Change: H254L
| Domain | Start | End | E-Value | Type |
|---|
|
RING
|
24 |
64 |
1.82e-7 |
SMART |
|
Pfam:BRCT_assoc
|
342 |
503 |
2.6e-69 |
PFAM |
|
low complexity region
|
1173 |
1185 |
N/A |
INTRINSIC |
|
Blast:BRCT
|
1343 |
1406 |
2e-16 |
BLAST |
|
low complexity region
|
1555 |
1575 |
N/A |
INTRINSIC |
|
BRCT
|
1587 |
1669 |
3.87e-11 |
SMART |
|
BRCT
|
1700 |
1787 |
3.42e-12 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000131460
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000142086
|
| SMART Domains |
Protein: ENSMUSP00000139813
Gene: ENSMUSG00000017146
| Domain | Start | End | E-Value | Type |
|---|
|
RING
|
24 |
64 |
8.6e-10 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000188168
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000191198
|
| SMART Domains |
Protein: ENSMUSP00000139737
Gene: ENSMUSG00000017146
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:EIN3
|
1 |
146 |
3.5e-18 |
PFAM |
|
| Coding Region Coverage |
- 1x: 98.8%
- 3x: 97.7%
- 10x: 94.4%
- 20x: 86.3%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009]
PHENOTYPE: Homozygous null mutants are embryonic lethal with abnormalities including growth retardation, neural tube defects, and mesoderm abnormalities; conditional mutations cause genetic instability and enhanced tumor formation; mutants with truncated BRCA1 protein survive, have a kinky tail, pigmentation anomalies, male infertility and increased tumor incidence. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 20 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Amer3 |
A |
T |
1: 34,588,389 |
T570S |
probably benign |
Het |
| Ank3 |
A |
T |
10: 69,534,280 |
K20I |
possibly damaging |
Het |
| Bmp10 |
G |
A |
6: 87,433,758 |
E178K |
probably benign |
Het |
| Cdon |
C |
T |
9: 35,504,189 |
S1241L |
possibly damaging |
Het |
| Cnst |
C |
A |
1: 179,579,486 |
P33T |
possibly damaging |
Het |
| Dnhd1 |
A |
G |
7: 105,720,124 |
Y4318C |
probably damaging |
Het |
| Farp1 |
G |
A |
14: 121,257,966 |
W611* |
probably null |
Het |
| Fst |
C |
T |
13: 114,454,279 |
|
probably benign |
Het |
| Gapvd1 |
A |
G |
2: 34,706,802 |
L714P |
probably damaging |
Het |
| Hectd4 |
T |
G |
5: 121,353,695 |
L3732R |
possibly damaging |
Het |
| Lox |
A |
G |
18: 52,528,819 |
Y171H |
probably damaging |
Het |
| Magi3 |
T |
A |
3: 104,015,058 |
K1448* |
probably null |
Het |
| Med12l |
T |
A |
3: 59,037,738 |
I128N |
probably benign |
Het |
| Pkd1l2 |
T |
C |
8: 117,054,934 |
T791A |
possibly damaging |
Het |
| Prrt4 |
A |
G |
6: 29,169,951 |
V834A |
possibly damaging |
Het |
| Ptprz1 |
A |
G |
6: 23,001,729 |
S1273G |
probably benign |
Het |
| Slc13a4 |
A |
C |
6: 35,271,662 |
F517V |
probably damaging |
Het |
| Treh |
T |
C |
9: 44,685,305 |
V452A |
probably benign |
Het |
| Vmn2r83 |
T |
A |
10: 79,479,097 |
M393K |
probably damaging |
Het |
| Zfp931 |
T |
C |
2: 178,068,191 |
N134S |
probably benign |
Het |
|
| Other mutations in Brca1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01095:Brca1
|
APN |
11 |
101524369 |
missense |
possibly damaging |
0.71 |
|
IGL01598:Brca1
|
APN |
11 |
101524330 |
missense |
probably benign |
0.04 |
|
IGL01744:Brca1
|
APN |
11 |
101524176 |
missense |
possibly damaging |
0.73 |
|
IGL02128:Brca1
|
APN |
11 |
101530982 |
unclassified |
probably benign |
|
|
IGL02377:Brca1
|
APN |
11 |
101524323 |
missense |
probably benign |
0.01 |
|
IGL02701:Brca1
|
APN |
11 |
101525235 |
missense |
probably damaging |
1.00 |
|
IGL02732:Brca1
|
APN |
11 |
101492219 |
missense |
probably benign |
0.07 |
|
IGL02935:Brca1
|
APN |
11 |
101489867 |
missense |
probably benign |
0.00 |
|
IGL02940:Brca1
|
APN |
11 |
101489912 |
missense |
probably benign |
0.00 |
|
IGL03198:Brca1
|
APN |
11 |
101512711 |
splice site |
probably benign |
|
|
BB002:Brca1
|
UTSW |
11 |
101508146 |
missense |
probably benign |
0.01 |
|
BB009:Brca1
|
UTSW |
11 |
101540017 |
missense |
possibly damaging |
0.85 |
|
BB012:Brca1
|
UTSW |
11 |
101508146 |
missense |
probably benign |
0.01 |
|
BB019:Brca1
|
UTSW |
11 |
101540017 |
missense |
possibly damaging |
0.85 |
|
PIT4142001:Brca1
|
UTSW |
11 |
101522422 |
unclassified |
probably benign |
|
|
R0048:Brca1
|
UTSW |
11 |
101524977 |
missense |
possibly damaging |
0.94 |
|
R0048:Brca1
|
UTSW |
11 |
101524977 |
missense |
possibly damaging |
0.94 |
|
R0109:Brca1
|
UTSW |
11 |
101531090 |
missense |
possibly damaging |
0.85 |
|
R0109:Brca1
|
UTSW |
11 |
101531090 |
missense |
possibly damaging |
0.85 |
|
R0144:Brca1
|
UTSW |
11 |
101526121 |
missense |
probably damaging |
1.00 |
|
R0336:Brca1
|
UTSW |
11 |
101523993 |
missense |
probably benign |
0.04 |
|
R0448:Brca1
|
UTSW |
11 |
101508221 |
missense |
possibly damaging |
0.93 |
|
R0595:Brca1
|
UTSW |
11 |
101524887 |
missense |
probably benign |
0.27 |
|
R0613:Brca1
|
UTSW |
11 |
101508210 |
missense |
probably benign |
0.18 |
|
R0863:Brca1
|
UTSW |
11 |
101524770 |
missense |
probably benign |
0.36 |
|
R0940:Brca1
|
UTSW |
11 |
101532143 |
missense |
possibly damaging |
0.73 |
|
R0962:Brca1
|
UTSW |
11 |
101525366 |
missense |
possibly damaging |
0.46 |
|
R1365:Brca1
|
UTSW |
11 |
101501996 |
missense |
probably benign |
|
|
R1467:Brca1
|
UTSW |
11 |
101531107 |
unclassified |
probably benign |
|
|
R1484:Brca1
|
UTSW |
11 |
101529812 |
missense |
possibly damaging |
0.86 |
|
R1530:Brca1
|
UTSW |
11 |
101524695 |
missense |
probably damaging |
1.00 |
|
R1645:Brca1
|
UTSW |
11 |
101510053 |
missense |
probably benign |
0.00 |
|
R1682:Brca1
|
UTSW |
11 |
101525565 |
missense |
probably damaging |
0.98 |
|
R1687:Brca1
|
UTSW |
11 |
101489840 |
missense |
probably benign |
|
|
R1694:Brca1
|
UTSW |
11 |
101532099 |
missense |
probably damaging |
0.98 |
|
R1695:Brca1
|
UTSW |
11 |
101524455 |
missense |
probably damaging |
0.97 |
|
R1762:Brca1
|
UTSW |
11 |
101532018 |
critical splice donor site |
probably null |
|
|
R1868:Brca1
|
UTSW |
11 |
101498013 |
missense |
probably benign |
|
|
R1973:Brca1
|
UTSW |
11 |
101526403 |
missense |
probably benign |
0.22 |
|
R2034:Brca1
|
UTSW |
11 |
101489849 |
missense |
probably benign |
|
|
R2106:Brca1
|
UTSW |
11 |
101524977 |
missense |
possibly damaging |
0.94 |
|
R4089:Brca1
|
UTSW |
11 |
101524176 |
missense |
possibly damaging |
0.73 |
|
R4194:Brca1
|
UTSW |
11 |
101525287 |
missense |
probably benign |
0.02 |
|
R4571:Brca1
|
UTSW |
11 |
101517366 |
missense |
probably benign |
0.00 |
|
R4735:Brca1
|
UTSW |
11 |
101492175 |
splice site |
probably null |
|
|
R4789:Brca1
|
UTSW |
11 |
101523932 |
missense |
probably benign |
0.00 |
|
R4920:Brca1
|
UTSW |
11 |
101524959 |
missense |
probably damaging |
1.00 |
|
R4939:Brca1
|
UTSW |
11 |
101508050 |
missense |
probably benign |
|
|
R4997:Brca1
|
UTSW |
11 |
101524333 |
missense |
probably damaging |
0.96 |
|
R5458:Brca1
|
UTSW |
11 |
101517285 |
missense |
possibly damaging |
0.53 |
|
R5778:Brca1
|
UTSW |
11 |
101525301 |
missense |
possibly damaging |
0.47 |
|
R6051:Brca1
|
UTSW |
11 |
101524246 |
missense |
probably damaging |
1.00 |
|
R6505:Brca1
|
UTSW |
11 |
101523541 |
missense |
probably benign |
0.03 |
|
R6548:Brca1
|
UTSW |
11 |
101524765 |
missense |
probably damaging |
1.00 |
|
R6971:Brca1
|
UTSW |
11 |
101534005 |
missense |
probably benign |
0.18 |
|
R7091:Brca1
|
UTSW |
11 |
101526427 |
missense |
probably benign |
0.00 |
|
R7246:Brca1
|
UTSW |
11 |
101523378 |
missense |
probably benign |
0.00 |
|
R7417:Brca1
|
UTSW |
11 |
101524981 |
missense |
probably damaging |
1.00 |
|
R7861:Brca1
|
UTSW |
11 |
101526422 |
missense |
possibly damaging |
0.87 |
|
R7925:Brca1
|
UTSW |
11 |
101508146 |
missense |
probably benign |
0.01 |
|
R7932:Brca1
|
UTSW |
11 |
101540017 |
missense |
possibly damaging |
0.85 |
|
R8003:Brca1
|
UTSW |
11 |
101524477 |
missense |
probably benign |
0.22 |
|
R8046:Brca1
|
UTSW |
11 |
101525470 |
missense |
probably benign |
0.03 |
|
R8306:Brca1
|
UTSW |
11 |
101525637 |
missense |
probably damaging |
1.00 |
|
R8483:Brca1
|
UTSW |
11 |
101525976 |
missense |
probably damaging |
0.99 |
|
R8685:Brca1
|
UTSW |
11 |
101489846 |
missense |
probably benign |
0.19 |
|
R9072:Brca1
|
UTSW |
11 |
101502480 |
critical splice donor site |
probably null |
|
|
R9073:Brca1
|
UTSW |
11 |
101502480 |
critical splice donor site |
probably null |
|
|
R9486:Brca1
|
UTSW |
11 |
101523694 |
missense |
probably benign |
0.00 |
|
R9505:Brca1
|
UTSW |
11 |
101512766 |
missense |
probably benign |
0.00 |
|
R9616:Brca1
|
UTSW |
11 |
101525857 |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- GCTATGCCAGGCTGTTTGCTTTTATT -3'
(R):5'- AGCTCCTCTAAAGAAGCCACTGGA -3'
Sequencing Primer
(F):5'- ATTACAGAATTCAGCCTTTTCTGC -3'
(R):5'- GTGAGTTTTCTGAGGGCATAAGAAAC -3'
|
| Posted On |
2014-03-17 |
Incidental Mutation