rs13130508

Positions:

• chr4-46084931-T-C

Variant summary

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

The ENST00000295452.5(GABRG1):​c.254-878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 151,668 control chromosomes in the GnomAD database, including 211 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 0.041 (211 hom., cov: 32)
• Consequence: GABRG1 ENST00000295452.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.254-878A>G		intron_variant		ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.254-878A>G		intron_variant		1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6267 AN: 151550 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0336

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

GnomAD4 genome AF: 0.0414 AC: 6281 AN: 151668 Hom.: 211 Cov.: 32 AF XY: 0.0446 AC XY: 3302 AN XY: 74118

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.0768

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0355 Hom.: 13

Bravo AF: 0.0417

Asia WGS AF: 0.0160 AC: 56 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.65

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: rs13130508; hg19: chr4-46086948;