7-2538059-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152743.4(BRAT1):c.*10G>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 0.000378 in 1,541,596 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: BRAT1 NM_152743.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-2538059-C-G is Benign according to our data. Variant chr7-2538059-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1189594.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAT1	NM_152743.4	c.*10G>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.*10G>C		3_prime_UTR_variant	14/14	1	NM_152743.4	P1
BRAT1	ENST00000467558.5	n.4262G>C		non_coding_transcript_exon_variant	10/10	5
BRAT1	ENST00000469750.5	n.5048G>C		non_coding_transcript_exon_variant	11/11	2
BRAT1	ENST00000493232.5	n.5182G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000385 AC: 76 AN: 197386 Hom.: 0 AF XY: 0.000488 AC XY: 52 AN XY: 106552

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00123

Gnomad FIN exome AF: 0.000163

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.000633

GnomAD4 exome AF: 0.000384 AC: 534 AN: 1389248 Hom.: 2 Cov.: 31 AF XY: 0.000452 AC XY: 308 AN XY: 681314

Gnomad4 AFR exome AF: 0.000158

Gnomad4 AMR exome AF: 0.000243

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000774

Gnomad4 SAS exome AF: 0.00157

Gnomad4 FIN exome AF: 0.000180

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152348 Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29 AN XY: 74496

Gnomad4 AFR AF: 0.0000721

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000298

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 04, 2023

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.87
Dann	Benign	0.44

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: rs190232808; hg19: chr7-2577693; COSMIC: COSV100500657; COSMIC: COSV100500657;