Variant chr4-46250306-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000807.4(GABRA2):c.*2T>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 0.00235 in 1,606,202 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 43 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

GABRA2
NM_000807.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.529

Variant links:

Genes affected

GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

GABRA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-46250306-A-T is Benign according to our data. Variant chr4-46250306-A-T is described in ClinVar as [Benign]. Clinvar id is 3038829.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1882/151744) while in subpopulation AFR AF= 0.043 (1784/41482). AF 95% confidence interval is 0.0413. There are 43 homozygotes in gnomad4. There are 909 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1882 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4 linkuse as main transcript	c.*2T>A		3_prime_UTR_variant	10/10	ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9 linkuse as main transcript	c.*2T>A		3_prime_UTR_variant	10/10	1	NM_000807.4	P2	P47869-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1858

AN:

151626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00435

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00816

GnomAD3 exomes

AF:

0.00313

AC:

771

AN:

246274

Hom.:

AF XY:

0.00225

AC XY:

300

AN XY:

133350

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000718

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00131

AC:

1899

AN:

1454458

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

795

AN XY:

723374

show subpopulations

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.00382

GnomAD4 genome

AF:

0.0124

AC:

1882

AN:

151744

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

909

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.0430

Gnomad4 AMR

AF:

0.00435

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00807

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00549

AC:

AN:

3476

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GABRA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

DANN

Benign

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over