rs752297498

Variant names:

• chr7-2541709-C-T
• rs752297498
• NM_152743.4:c.1134+9G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000340611.9(BRAT1):​c.1134+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,602,598 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: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: BRAT1 ENST00000340611.9 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.405
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-2541709-C-T is Benign according to our data. Variant chr7-2541709-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 472929.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340611.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	NM_152743.4	MANE Select	c.1134+9G>A		intron	N/A	NP_689956.2
	BRAT1	NM_001350626.2		c.1134+9G>A		intron	N/A	NP_001337555.1
	BRAT1	NM_001350627.2		c.609+9G>A		intron	N/A	NP_001337556.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	ENST00000340611.9	TSL:1 MANE Select	c.1134+9G>A		intron	N/A	ENSP00000339637.4
	BRAT1	ENST00000467558.5	TSL:5	n.1416+9G>A		intron	N/A
	BRAT1	ENST00000469750.5	TSL:2	n.2616+9G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000531 AC: 12 AN: 225930 AF XY: 0.0000323

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000277

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000601

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000198

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 37 AN: 1450396 Hom.: 0 Cov.: 32 AF XY: 0.0000208 AC XY: 15 AN XY: 720952

African (AFR) AF: 0.0000599 AC: 2 AN: 33368

American (AMR) AF: 0.000324 AC: 14 AN: 43144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39354

South Asian (SAS) AF: 0.00 AC: 0 AN: 84856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5588

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1108138

Other (OTH) AF: 0.0000334 AC: 2 AN: 59924

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74348

African (AFR) AF: 0.0000965 AC: 4 AN: 41434

American (AMR) AF: 0.000654 AC: 10 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	BRAT1-related disorder (1)
-	-	1	Neonatal-onset encephalopathy with rigidity and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		-0.41

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

Other links and lift over

dbSNP: rs752297498; hg19: chr7-2581343; COSMIC: COSV61396474; COSMIC: COSV61396474;