rs6972204

Positions:

• chr7-2542818-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152743.4(BRAT1):​c.923+386A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 173,482 control chromosomes in the GnomAD database, including 2,163 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1958 hom., cov: 32)
  • Exomes 𝑓: 0.12 (205 hom.)
• Consequence: BRAT1 NM_152743.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAT1	NM_152743.4	c.923+386A>G		intron_variant		ENST00000340611.9	NP_689956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9	c.923+386A>G		intron_variant		1	NM_152743.4	ENSP00000339637	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23340 AN: 151854 Hom.: 1955 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.119 AC: 2561 AN: 21510 Hom.: 205 Cov.: 0 AF XY: 0.113 AC XY: 1253 AN XY: 11126

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0550

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.154 AC: 23368 AN: 151972 Hom.: 1958 Cov.: 32 AF XY: 0.154 AC XY: 11455 AN XY: 74290

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.0914

Gnomad4 SAS AF: 0.0695

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.153

Alfa AF: 0.142 Hom.: 323

Bravo AF: 0.157

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6972204; hg19: chr7-2582452; COSMIC: COSV61394517; COSMIC: COSV61394517;