rs6972204

Variant names:

• chr7-2542818-T-C
• rs6972204
• NM_152743.4:c.923+386A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350626.2(BRAT1):​c.923+386A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 173,482 control chromosomes in the GnomAD database, including 2,163 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1958 hom., cov: 32)
  • Exomes 𝑓: 0.12 (205 hom.)
• Consequence: BRAT1 NM_001350626.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350626.2. 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.923+386A>G		intron	N/A	NP_689956.2
	BRAT1	NM_001350626.2		c.923+386A>G		intron	N/A	NP_001337555.1
	BRAT1	NM_001350627.2		c.398+386A>G		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.923+386A>G		intron	N/A	ENSP00000339637.4
	BRAT1	ENST00000890463.1		c.923+386A>G		intron	N/A	ENSP00000560522.1
	BRAT1	ENST00000917322.1		c.920+386A>G		intron	N/A	ENSP00000587381.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23340 AN: 151854 Hom.: 1955 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.119 AC: 2561 AN: 21510 Hom.: 205 Cov.: 0 AF XY: 0.113 AC XY: 1253 AN XY: 11126

African (AFR) AF: 0.204 AC: 82 AN: 402

American (AMR) AF: 0.138 AC: 262 AN: 1892

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 65 AN: 476

East Asian (EAS) AF: 0.145 AC: 68 AN: 470

South Asian (SAS) AF: 0.0550 AC: 115 AN: 2092

European-Finnish (FIN) AF: 0.152 AC: 133 AN: 876

Middle Eastern (MID) AF: 0.163 AC: 280 AN: 1718

European-Non Finnish (NFE) AF: 0.113 AC: 1393 AN: 12364

Other (OTH) AF: 0.134 AC: 163 AN: 1220

GnomAD4 genome AF: 0.154 AC: 23368 AN: 151972 Hom.: 1958 Cov.: 32 AF XY: 0.154 AC XY: 11455 AN XY: 74290

African (AFR) AF: 0.218 AC: 9040 AN: 41430

American (AMR) AF: 0.144 AC: 2200 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3470

East Asian (EAS) AF: 0.0914 AC: 470 AN: 5142

South Asian (SAS) AF: 0.0695 AC: 335 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2006 AN: 10582

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8191 AN: 67942

Other (OTH) AF: 0.153 AC: 323 AN: 2108

Alfa AF: 0.145 Hom.: 390

Bravo AF: 0.157

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6972204; hg19: chr7-2582452; COSMIC: COSV61394517; COSMIC: COSV61394517;