7-2538055-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152743.4(BRAT1):c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,528,528 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (9 hom.)
• Consequence: BRAT1 NM_152743.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230

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=-0.89).
• BP6: Variant 7-2538055-G-A is Benign according to our data. Variant chr7-2538055-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1199781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00644 (981/152358) while in subpopulation AFR AF= 0.0225 (936/41584). AF 95% confidence interval is 0.0213. There are 14 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAT1	ENST00000340611.9	c.*14C>T		3_prime_UTR_variant	14/14	1	NM_152743.4	P1
BRAT1	ENST00000467558.5	n.4266C>T		non_coding_transcript_exon_variant	10/10	5
BRAT1	ENST00000469750.5	n.5052C>T		non_coding_transcript_exon_variant	11/11	2
BRAT1	ENST00000493232.5	n.5186C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.00642 AC: 978 AN: 152240 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00181 AC: 337 AN: 186176 Hom.: 3 AF XY: 0.00125 AC XY: 125 AN XY: 100372

Gnomad AFR exome AF: 0.0227

Gnomad AMR exome AF: 0.000649

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000567

Gnomad NFE exome AF: 0.0000459

Gnomad OTH exome AF: 0.000459

GnomAD4 exome AF: 0.000605 AC: 833 AN: 1376170 Hom.: 9 Cov.: 29 AF XY: 0.000524 AC XY: 353 AN XY: 673524

Gnomad4 AFR exome AF: 0.0227

Gnomad4 AMR exome AF: 0.000821

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000685

Gnomad4 FIN exome AF: 0.0000202

Gnomad4 NFE exome AF: 0.0000281

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00644 AC: 981 AN: 152358 Hom.: 14 Cov.: 33 AF XY: 0.00627 AC XY: 467 AN XY: 74508

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00364 Hom.: 2

Bravo AF: 0.00734

Asia WGS AF: 0.000577 AC: 2 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

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.40

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: rs140062589; hg19: chr7-2577689;