rs8176306

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007294.4(BRCA1):​c.5333-134C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 816,116 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0026 ( 7 hom. )

Consequence

BRCA1
NM_007294.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.239
Variant links:
Genes affected
BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. 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 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-43049328-G-T is Benign according to our data. Variant chr17-43049328-G-T is described in ClinVar as [Benign]. Clinvar id is 491110.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-43049328-G-T is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAdExome4 at 7 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRCA1NM_007294.4 linkuse as main transcriptc.5333-134C>A intron_variant ENST00000357654.9 NP_009225.1 P38398-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRCA1ENST00000357654.9 linkuse as main transcriptc.5333-134C>A intron_variant 1 NM_007294.4 ENSP00000350283.3 P38398-1

Frequencies

GnomAD3 genomes
AF:
0.00194
AC:
295
AN:
152144
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000676
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00395
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00265
Gnomad OTH
AF:
0.00336
GnomAD4 exome
AF:
0.00261
AC:
1731
AN:
663854
Hom.:
7
AF XY:
0.00268
AC XY:
945
AN XY:
352584
show subpopulations
Gnomad4 AFR exome
AF:
0.000498
Gnomad4 AMR exome
AF:
0.00172
Gnomad4 ASJ exome
AF:
0.0000492
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00336
Gnomad4 FIN exome
AF:
0.00549
Gnomad4 NFE exome
AF:
0.00270
Gnomad4 OTH exome
AF:
0.00299
GnomAD4 genome
AF:
0.00193
AC:
294
AN:
152262
Hom.:
1
Cov.:
31
AF XY:
0.00203
AC XY:
151
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000674
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00395
Gnomad4 NFE
AF:
0.00265
Gnomad4 OTH
AF:
0.00332
Alfa
AF:
0.00209
Hom.:
0
Bravo
AF:
0.00186
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthMay 10, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.7
DANN
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8176306; hg19: chr17-41201345; API