rs2221020

Positions:

• chr4-46101548-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.105-4199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,388 control chromosomes in the GnomAD database, including 27,231 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 0.59 (27231 hom., cov: 30)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.105-4199G>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.105-4199G>A		intron_variant		1	NM_173536.4	ENSP00000295452	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 88900 AN: 151270 Hom.: 27188 Cov.: 30

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.588 AC: 89002 AN: 151388 Hom.: 27231 Cov.: 30 AF XY: 0.584 AC XY: 43158 AN XY: 73930

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.548

Alfa AF: 0.563 Hom.: 8542

Bravo AF: 0.591

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.37

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: rs2221020; hg19: chr4-46103565;