7-2537850-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152743.4(BRAT1):c.*219C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 697,314 control chromosomes in the GnomAD database, including 126 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 (18 hom., cov: 33)
  • Exomes 𝑓: 0.012 (108 hom.)
• Consequence: BRAT1 NM_152743.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0160

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-2537850-G-T is Benign according to our data. Variant chr7-2537850-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1186082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAT1	NM_152743.4	c.*219C>A		3_prime_UTR_variant	14/14	ENST00000340611.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAT1	ENST00000340611.9	c.*219C>A		3_prime_UTR_variant	14/14	1	NM_152743.4	P1
BRAT1	ENST00000467558.5			downstream_gene_variant		5
BRAT1	ENST00000469750.5			downstream_gene_variant		2
BRAT1	ENST00000493232.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1935 AN: 152214 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00794

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0120 AC: 6520 AN: 544982 Hom.: 108 Cov.: 8 AF XY: 0.0121 AC XY: 3264 AN XY: 269508

Gnomad4 AFR exome AF: 0.0195

Gnomad4 AMR exome AF: 0.00798

Gnomad4 ASJ exome AF: 0.0146

Gnomad4 EAS exome AF: 0.0598

Gnomad4 SAS exome AF: 0.0321

Gnomad4 FIN exome AF: 0.00363

Gnomad4 NFE exome AF: 0.00813

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0127 AC: 1936 AN: 152332 Hom.: 18 Cov.: 33 AF XY: 0.0131 AC XY: 974 AN XY: 74502

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.00794

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0101 Hom.: 1

Bravo AF: 0.0128

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neonatal-onset encephalopathy with rigidity and seizures;C4748032:Neurodevelopmental disorder with cerebellar atrophy and with or without seizures Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 16, 2021

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.70
Dann	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145828184; hg19: chr7-2577484;