4-46092242-C-T

Position:

• chr4-46092242-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295452.5(GABRG1):​c.253+4959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,672 control chromosomes in the GnomAD database, including 19,327 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 0.50 (19327 hom., cov: 32)
• Consequence: GABRG1 ENST00000295452.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

GABRG1 (HGNC:4086): (gamma-aminobutyric acid type A receptor subunit gamma1) The protein encoded by this gene belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission by binding to the benzodiazepine receptor and opening an integral chloride channel. This gene is clustered with three other family members on chromosome 4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.253+4959G>A		intron_variant		ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.253+4959G>A		intron_variant		1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75862 AN: 151552 Hom.: 19305 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.501 AC: 75938 AN: 151672 Hom.: 19327 Cov.: 32 AF XY: 0.495 AC XY: 36691 AN XY: 74078

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.482

Alfa AF: 0.362 Hom.: 938

Bravo AF: 0.501

Asia WGS AF: 0.358 AC: 1232 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs6824361; hg19: chr4-46094259;