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rs143192367

chr7-2543631-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_152743.4(BRAT1):c.762C>T(p.Pro254=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,536,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.61
Variant links:
Genes affected
BRAT1 (HGNC:21701): (BRCA1 associated ATM activator 1) The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. [provided by RefSeq, Mar 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-2543631-G-A is Benign according to our data. Variant chr7-2543631-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.61 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BRAT1NM_152743.4 linkuse as main transcriptc.762C>T p.Pro254= synonymous_variant 5/14 ENST00000340611.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRAT1ENST00000340611.9 linkuse as main transcriptc.762C>T p.Pro254= synonymous_variant 5/141 NM_152743.4 P1Q6PJG6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000230
AC:
35
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00385
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000361
AC:
71
AN:
196716
Hom.:
0
AF XY:
0.000304
AC XY:
32
AN XY:
105180
show subpopulations
Gnomad AFR exome
AF:
0.000134
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00347
Gnomad SAS exome
AF:
0.000304
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000553
Gnomad OTH exome
AF:
0.000219
GnomAD4 exome
AF:
0.000126
AC:
174
AN:
1384476
Hom.:
1
Cov.:
33
AF XY:
0.000122
AC XY:
83
AN XY:
678714
show subpopulations
Gnomad4 AFR exome
AF:
0.000127
Gnomad4 AMR exome
AF:
0.0000273
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00177
Gnomad4 SAS exome
AF:
0.000558
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.000579
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000230
AC:
35
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00386
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000276
Hom.:
0
Bravo
AF:
0.000230
Asia WGS
AF:
0.00895
AC:
31
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Neonatal-onset encephalopathy with rigidity and seizures Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJan 24, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
0.041
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs143192367; hg19: chr7-2583265; COSMIC: COSV61396362; COSMIC: COSV61396362; API