4-46114415-A-G

Position:

• chr4-46114415-A-G

Variant summary

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

The NM_173536.4(GABRG1):​c.104+9395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 150,754 control chromosomes in the GnomAD database, including 14,407 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 0.43 (14407 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.104+9395T>C		intron_variant		ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.104+9395T>C		intron_variant		1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 64765 AN: 150642 Hom.: 14398 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.430 AC: 64817 AN: 150754 Hom.: 14407 Cov.: 31 AF XY: 0.425 AC XY: 31277 AN XY: 73614

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.422

Alfa AF: 0.464 Hom.: 7820

Bravo AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.73

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: rs12511372; hg19: chr4-46116432;