chr7-2538613-G-C

Position:

• chr7-2538613-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152743.4(BRAT1):​c.1922C>G​(p.Ala641Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A641V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRAT1 NM_152743.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04603821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAT1	NM_152743.4	c.1922C>G	p.Ala641Gly	missense_variant	14/14	ENST00000340611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAT1	ENST00000340611.9	c.1922C>G	p.Ala641Gly	missense_variant	14/14	1	NM_152743.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.000195 AC: 43 AN: 220304 Hom.: 0 AF XY: 0.000236 AC XY: 29 AN XY: 122754

Gnomad AFR exome AF: 0.000224

Gnomad AMR exome AF: 0.000330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000581

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000280

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000236 AC: 34 AN: 1442738 Hom.: 0 Cov.: 70 AF XY: 0.0000237 AC XY: 17 AN XY: 718032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000410

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000259

Gnomad4 NFE exome AF: 0.00000901

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.000462 AC: 55

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.28
DANN	Benign	0.66
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.095	T
Polyphen		0.31	B
Vest4		0.16
MutPred		0.48		Loss of helix (P = 0.0196);
MVP		0.048
MPC		0.069
ClinPred		0.058	T
GERP RS		-11
Varity_R		0.090
gMVP		0.13

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

Other links and lift over

dbSNP: rs113030000; hg19: chr7-2578247;