rs7807895

chr7-2541413-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_152743.4(BRAT1):c.1206C>T(p.Asp402=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,596,454 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (43 hom.)
• Consequence: BRAT1 NM_152743.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.02

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-2541413-G-A is Benign according to our data. Variant chr7-2541413-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 446894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1975/152284) while in subpopulation AFR AF= 0.0437 (1817/41542). AF 95% confidence interval is 0.0421. There are 43 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAT1	NM_152743.4	c.1206C>T	p.Asp402=	synonymous_variant	9/14	ENST00000340611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAT1	ENST00000340611.9	c.1206C>T	p.Asp402=	synonymous_variant	9/14	1	NM_152743.4	P1
BRAT1	ENST00000467558.5	n.1488C>T		non_coding_transcript_exon_variant	7/10	5
BRAT1	ENST00000469750.5	n.2688C>T		non_coding_transcript_exon_variant	7/11	2
BRAT1	ENST00000493232.5	n.2607C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1973 AN: 152166 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00308 AC: 653 AN: 212330 Hom.: 13 AF XY: 0.00230 AC XY: 268 AN XY: 116484

Gnomad AFR exome AF: 0.0434

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000284

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000140

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00134 AC: 1940 AN: 1444170 Hom.: 43 Cov.: 33 AF XY: 0.00119 AC XY: 853 AN XY: 717228

Gnomad4 AFR exome AF: 0.0446

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000272

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000769

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.0130 AC: 1975 AN: 152284 Hom.: 43 Cov.: 33 AF XY: 0.0125 AC XY: 928 AN XY: 74464

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00238 Hom.: 3

Bravo AF: 0.0148

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 28, 2017

- -

Neonatal-onset encephalopathy with rigidity and seizures Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.7
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs7807895; hg19: chr7-2581047;