4-46053461-C-T

Position:

• chr4-46053461-C-T

Variant summary

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

The ENST00000295452.5(GABRG1):​c.917-1823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 151,962 control chromosomes in the GnomAD database, including 62,181 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 0.90 (62181 hom., cov: 32)
• Consequence: GABRG1 ENST00000295452.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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 = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.917-1823G>A		intron_variant		ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.530-1823G>A		intron_variant			XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.917-1823G>A		intron_variant		1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137134 AN: 151844 Hom.: 62129 Cov.: 32

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.903 AC: 137246 AN: 151962 Hom.: 62181 Cov.: 32 AF XY: 0.904 AC XY: 67150 AN XY: 74264

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.903

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.899

Alfa AF: 0.874 Hom.: 64337

Bravo AF: 0.904

Asia WGS AF: 0.903 AC: 3137 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.53
DANN	Benign	0.22

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: rs993677; hg19: chr4-46055478;