7-2538327-C-G

Variant summary

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

The NM_152743.4(BRAT1):ā€‹c.2208G>Cā€‹(p.Leu736Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,756 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: not found (cov: 34)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

BRAT1
NM_152743.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.431
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
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 7-2538327-C-G is Benign according to our data. Variant chr7-2538327-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2812468.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.431 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRAT1NM_152743.4 linkc.2208G>C p.Leu736Leu synonymous_variant Exon 14 of 14 ENST00000340611.9 NP_689956.2 Q6PJG6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRAT1ENST00000340611.9 linkc.2208G>C p.Leu736Leu synonymous_variant Exon 14 of 14 1 NM_152743.4 ENSP00000339637.4 Q6PJG6-1
BRAT1ENST00000467558.5 linkn.3994G>C non_coding_transcript_exon_variant Exon 10 of 10 5
BRAT1ENST00000469750.5 linkn.4780G>C non_coding_transcript_exon_variant Exon 11 of 11 2
BRAT1ENST00000493232.5 linkn.4914G>C non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000805
AC:
2
AN:
248466
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460756
Hom.:
0
Cov.:
66
AF XY:
0.00000275
AC XY:
2
AN XY:
726700
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

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
Nov 06, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.17
DANN
Benign
0.42
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

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: rs61753093; hg19: chr7-2577961; API