chr7-2545020-C-T

Variant names:

• chr7-2545020-C-T
• rs749992319
• NM_152743.4:c.319G>A
• BRAT1 p.Gly107Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152743.4(BRAT1):​c.319G>A​(p.Gly107Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,531,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: BRAT1 NM_152743.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 3.68
• Publications: 1 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• neurodevelopmental disorder with cerebellar atrophy and with or without seizures

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152743.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	NM_152743.4	MANE Select	c.319G>A	p.Gly107Arg	missense	Exon 4 of 14	NP_689956.2	Q6PJG6-1
	BRAT1	NM_001350626.2		c.319G>A	p.Gly107Arg	missense	Exon 4 of 14	NP_001337555.1
	BRAT1	NM_001350627.2		c.-95-1058G>A		intron	N/A	NP_001337556.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	ENST00000340611.9	TSL:1 MANE Select	c.319G>A	p.Gly107Arg	missense	Exon 4 of 14	ENSP00000339637.4	Q6PJG6-1
	BRAT1	ENST00000890463.1		c.319G>A	p.Gly107Arg	missense	Exon 4 of 16	ENSP00000560522.1
	BRAT1	ENST00000917322.1		c.316G>A	p.Gly106Arg	missense	Exon 4 of 16	ENSP00000587381.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152190 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 0.0000122 AC: 2 AN: 164030 AF XY: 0.0000225

Gnomad AFR exome AF: 0.0000907

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000125 AC: 172 AN: 1379126 Hom.: 0 Cov.: 31 AF XY: 0.000120 AC XY: 81 AN XY: 677638

African (AFR) AF: 0.00 AC: 0 AN: 30694

American (AMR) AF: 0.00 AC: 0 AN: 31320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22430

East Asian (EAS) AF: 0.00 AC: 0 AN: 36964

South Asian (SAS) AF: 0.00 AC: 0 AN: 75540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.000156 AC: 167 AN: 1070644

Other (OTH) AF: 0.0000880 AC: 5 AN: 56800

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152190 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.0000483 AC: 2 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Neonatal-onset encephalopathy with rigidity and seizures (2)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.026	D
Varity_R		0.075
gMVP		0.56
Mutation Taster		=93/7	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs749992319;

hg19: chr7-2584654;