4-46084043-T-C

Position:

• chr4-46084043-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173536.4(GABRG1):​c.264A>G​(p.Thr88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,563,678 control chromosomes in the GnomAD database, including 242,916 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 0.58 (26452 hom., cov: 31)
  • Exomes 𝑓: 0.55 (216464 hom.)
• Consequence: GABRG1 NM_173536.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG1	NM_173536.4	c.264A>G	p.Thr88=	synonymous_variant	3/9	ENST00000295452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG1	ENST00000295452.5	c.264A>G	p.Thr88=	synonymous_variant	3/9	1	NM_173536.4	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88121 AN: 151172 Hom.: 26409 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.548

GnomAD3 exomes AF: 0.515 AC: 115648 AN: 224378 Hom.: 31064 AF XY: 0.504 AC XY: 61010 AN XY: 121094

Gnomad AFR exome AF: 0.697

Gnomad AMR exome AF: 0.533

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.367

Gnomad SAS exome AF: 0.335

Gnomad FIN exome AF: 0.633

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.547 AC: 772281 AN: 1412388 Hom.: 216464 Cov.: 26 AF XY: 0.539 AC XY: 379010 AN XY: 703114

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.583 AC: 88233 AN: 151290 Hom.: 26452 Cov.: 31 AF XY: 0.579 AC XY: 42810 AN XY: 73882

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.545

Alfa AF: 0.550 Hom.: 46147

Bravo AF: 0.584

Asia WGS AF: 0.395 AC: 1375 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.1
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: rs976156; hg19: chr4-46086060; COSMIC: COSV54951415;