rs1948609

Positions:

• chr4-46060755-A-C
• chr4-46060755-A-G
• chr4-46060755-A-T

Variant summary

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

The NM_173536.4(GABRG1):​c.626-2133T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,770 control chromosomes in the GnomAD database, including 19,974 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 0.51 (19974 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.626-2133T>G		intron_variant		ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.239-2133T>G		intron_variant			XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.626-2133T>G		intron_variant		1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76629 AN: 151652 Hom.: 19938 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.506 AC: 76735 AN: 151770 Hom.: 19974 Cov.: 31 AF XY: 0.505 AC XY: 37427 AN XY: 74154

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.474

Alfa AF: 0.378 Hom.: 1428

Bravo AF: 0.507

Asia WGS AF: 0.394 AC: 1370 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.99
DANN	Benign	0.58

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: rs1948609; hg19: chr4-46062772;