7-2538057-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152743.4(BRAT1):c.*12G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,539,028 control chromosomes in the GnomAD database, including 20,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1520 hom., cov: 33)
  • Exomes 𝑓: 0.16 (18495 hom.)
• Consequence: BRAT1 NM_152743.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-2538057-C-G is Benign according to our data. Variant chr7-2538057-C-G is described in ClinVar as [Benign]. Clinvar id is 1253787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAT1	NM_152743.4	c.*12G>C		3_prime_UTR_variant	14/14	ENST00000340611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAT1	ENST00000340611.9	c.*12G>C		3_prime_UTR_variant	14/14	1	NM_152743.4	P1
BRAT1	ENST00000467558.5	n.4264G>C		non_coding_transcript_exon_variant	10/10	5
BRAT1	ENST00000469750.5	n.5050G>C		non_coding_transcript_exon_variant	11/11	2
BRAT1	ENST00000493232.5	n.5184G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18487 AN: 152104 Hom.: 1514 Cov.: 33

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0958

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.137 AC: 26844 AN: 195372 Hom.: 2309 AF XY: 0.136 AC XY: 14390 AN XY: 105422

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.0925

Gnomad EAS exome AF: 0.00193

Gnomad SAS exome AF: 0.0748

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.157 AC: 217664 AN: 1386806 Hom.: 18495 Cov.: 31 AF XY: 0.154 AC XY: 105007 AN XY: 679802

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.0924

Gnomad4 EAS exome AF: 0.00121

Gnomad4 SAS exome AF: 0.0791

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.122 AC: 18501 AN: 152222 Hom.: 1520 Cov.: 33 AF XY: 0.121 AC XY: 9037 AN XY: 74396

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.0746

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.115

Alfa AF: 0.135 Hom.: 349

Bravo AF: 0.115

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.072
Dann	Benign	0.27

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: rs1043294; hg19: chr7-2577691;