rs1478205274

Variant names:

• chr7-2542111-G-A
• rs1478205274
• NM_152743.4:c.1015+9C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2542111-G-A
• chr7-2542111-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152743.4(BRAT1):​c.1015+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: BRAT1 NM_152743.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920
• Publications: 0 publications found

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]

BRAT1 Gene-Disease associations (from GenCC):

• neonatal-onset encephalopathy with rigidity and seizures

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with cerebellar atrophy and with or without seizures

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-2542111-G-A is Benign according to our data. Variant chr7-2542111-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2060290.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAT1	NM_152743.4	c.1015+9C>T		intron_variant	Intron 7 of 13	ENST00000340611.9	NP_689956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAT1	ENST00000340611.9	c.1015+9C>T		intron_variant	Intron 7 of 13	1	NM_152743.4	ENSP00000339637.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373926 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 676126

African (AFR) AF: 0.00 AC: 0 AN: 30820

American (AMR) AF: 0.0000323 AC: 1 AN: 30984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22568

East Asian (EAS) AF: 0.00 AC: 0 AN: 36486

South Asian (SAS) AF: 0.00 AC: 0 AN: 75128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068350

Other (OTH) AF: 0.00 AC: 0 AN: 56650

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neonatal-onset encephalopathy with rigidity and seizures Benign:1

Sep 25, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.26
PhyloP100		-0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1478205274; hg19: chr7-2581745;