rs6447493

Positions:

• chr4-46040928-C-T

Variant summary

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

The NM_173536.4(GABRG1):​c.*60G>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 0.468 in 1,486,312 control chromosomes in the GnomAD database, including 165,779 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 (19826 hom., cov: 32)
  • Exomes 𝑓: 0.46 (145953 hom.)
• Consequence: GABRG1 NM_173536.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.*60G>A		3_prime_UTR_variant	9/9	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.*60G>A		3_prime_UTR_variant	7/7		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.*60G>A		3_prime_UTR_variant	9/9	1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76354 AN: 151608 Hom.: 19792 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.464 AC: 618645 AN: 1334584 Hom.: 145953 Cov.: 20 AF XY: 0.458 AC XY: 303824 AN XY: 662836

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.504 AC: 76458 AN: 151728 Hom.: 19826 Cov.: 32 AF XY: 0.503 AC XY: 37295 AN XY: 74132

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.472

Alfa AF: 0.484 Hom.: 4411

Bravo AF: 0.505

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.39

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: rs6447493; hg19: chr4-46042945; COSMIC: COSV54951607;