rs370935312

Positions:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152743.4(BRAT1):ā€‹c.1680T>Cā€‹(p.Tyr560Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., cov: 33)
Exomes š‘“: 0.000022 ( 0 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 7-2539269-A-G is Benign according to our data. Variant chr7-2539269-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 472952.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRAT1NM_152743.4 linkuse as main transcriptc.1680T>C p.Tyr560Tyr synonymous_variant 13/14 ENST00000340611.9 NP_689956.2 Q6PJG6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRAT1ENST00000340611.9 linkuse as main transcriptc.1680T>C p.Tyr560Tyr synonymous_variant 13/141 NM_152743.4 ENSP00000339637.4 Q6PJG6-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000243
AC:
6
AN:
247236
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134468
show subpopulations
Gnomad AFR exome
AF:
0.000190
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000903
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1459650
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
12
AN XY:
726108
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.0000945
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

Neonatal-onset encephalopathy with rigidity and seizures Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 08, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.097
DANN
Benign
0.22
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs370935312; hg19: chr7-2578903; API