Variant 5-161847218-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000023897.10(GABRA1):c.-441A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,258 control chromosomes in the GnomAD database, including 7,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7786 hom., cov: 30)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

GABRA1
ENST00000023897.10 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.768

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-161847218-A-G is Benign according to our data. Variant chr5-161847218-A-G is described in ClinVar as [Benign]. Clinvar id is 352585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105377696	XR_941158.4 linkuse as main transcript	n.74+3302T>C		intron_variant, non_coding_transcript_variant
GABRA1	NM_000806.5 linkuse as main transcript	c.-441A>G		5_prime_UTR_variant	1/11		NP_000797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA1	ENST00000023897.10 linkuse as main transcript	c.-441A>G		5_prime_UTR_variant	1/11	1		ENSP00000023897	P1
GABRA1	ENST00000638112.1 linkuse as main transcript	c.-496A>G		5_prime_UTR_variant	1/11	5		ENSP00000489839	P1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45049

AN:

151130

Hom.:

7771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.125

GnomAD4 genome

AF:

0.298

AC:

45095

AN:

151248

Hom.:

7786

Cov.:

AF XY:

0.300

AC XY:

22173

AN XY:

73850

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.388

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.233

Hom.:

3874

Bravo

AF:

0.309

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epilepsy, idiopathic generalized, susceptibility to, 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.054

DANN

Benign

0.32

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