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rs768272447

chr7-2541329-G-Achr7-2541329-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_152743.4(BRAT1):c.1290C>T(p.Leu430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000531 in 1,601,094 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 (★). Synonymous variant affecting the same amino acid position (i.e. L430L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13
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 -5 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=-0.68).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-2541329-G-A is Benign according to our data. Variant chr7-2541329-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 540187.Status of the report is criteria_provided_single_submitter, 1 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=-1.13 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BRAT1NM_152743.4 linkuse as main transcriptc.1290C>T p.Leu430= synonymous_variant 9/14 ENST00000340611.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRAT1ENST00000340611.9 linkuse as main transcriptc.1290C>T p.Leu430= synonymous_variant 9/141 NM_152743.4 P1Q6PJG6-1
BRAT1ENST00000467558.5 linkuse as main transcriptn.1572C>T non_coding_transcript_exon_variant 7/105
BRAT1ENST00000469750.5 linkuse as main transcriptn.2772C>T non_coding_transcript_exon_variant 7/112
BRAT1ENST00000493232.5 linkuse as main transcriptn.2691C>T non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000197
AC:
3
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000721
AC:
17
AN:
235808
Hom.:
0
AF XY:
0.0000926
AC XY:
12
AN XY:
129566
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000296
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000280
Gnomad SAS exome
AF:
0.000232
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000278
Gnomad OTH exome
AF:
0.000171
GnomAD4 exome
AF:
0.0000566
AC:
82
AN:
1448904
Hom.:
0
Cov.:
33
AF XY:
0.0000694
AC XY:
50
AN XY:
720934
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000479
Gnomad4 SAS exome
AF:
0.000396
Gnomad4 FIN exome
AF:
0.0000225
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.000150
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000197
AC:
3
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000340

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 testingInvitaeNov 27, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
0.14
Dann
Benign
0.65

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: rs768272447; hg19: chr7-2580963; COSMIC: COSV100500486; COSMIC: COSV100500486; API