Variant chr5-161847210-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000023897.10(GABRA1):c.-449G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 150,550 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.10 ( 0 hom. )

Consequence

GABRA1
ENST00000023897.10 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.380

Variant links:

Genes affected

GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRA1 links:

LOC105377696 (HGNC:):

LOC105377696 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-161847210-G-C is Benign according to our data. Variant chr5-161847210-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 352581.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105377696	XR_941158.4 linkuse as main transcript	n.74+3310C>G		intron_variant, non_coding_transcript_variant
GABRA1	NM_000806.5 linkuse as main transcript	c.-449G>C		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000023897.10 linkuse as main transcript	c.-449G>C		5_prime_UTR_variant	1/11	1		P1
GABRA1	ENST00000638112.1 linkuse as main transcript	c.-504G>C		5_prime_UTR_variant	1/11	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

317

AN:

150428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00185

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00530

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00329

Gnomad OTH

AF:

0.000972

GnomAD4 exome

AF:

0.100

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.125

GnomAD4 genome

AF:

0.00211

AC:

317

AN:

150540

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

157

AN XY:

73622

show subpopulations

Gnomad4 AFR

AF:

0.000123

Gnomad4 AMR

AF:

0.00184

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00530

Gnomad4 NFE

AF:

0.00329

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00137

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Epilepsy, idiopathic generalized, susceptibility to, 13

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

GABRA1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.69

DANN

Benign

0.55

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