NM_173536.4:c.*60G>A

Variant names:

• chr4-46040928-C-T
• rs6447493
• NM_173536.4:c.*60G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173536.4(GABRG1):​c.*60G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,486,312 control chromosomes in the GnomAD database, including 165,779 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 0.50 (19826 hom., cov: 32)
  • Exomes 𝑓: 0.46 (145953 hom.)
• Consequence: GABRG1 NM_173536.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 10 publications found

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]

GABRG1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173536.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	NM_173536.4	MANE Select	c.*60G>A		3_prime_UTR	Exon 9 of 9	NP_775807.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	ENST00000295452.5	TSL:1 MANE Select	c.*60G>A		3_prime_UTR	Exon 9 of 9	ENSP00000295452.4
	GABRG1	ENST00000964875.1		c.*60G>A		3_prime_UTR	Exon 7 of 7	ENSP00000634934.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76354 AN: 151608 Hom.: 19792 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.464 AC: 618645 AN: 1334584 Hom.: 145953 Cov.: 20 AF XY: 0.458 AC XY: 303824 AN XY: 662836

African (AFR) AF: 0.623 AC: 18411 AN: 29568

American (AMR) AF: 0.486 AC: 16574 AN: 34082

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 9319 AN: 21662

East Asian (EAS) AF: 0.325 AC: 12668 AN: 38938

South Asian (SAS) AF: 0.337 AC: 24636 AN: 73184

European-Finnish (FIN) AF: 0.541 AC: 26580 AN: 49106

Middle Eastern (MID) AF: 0.300 AC: 1548 AN: 5168

European-Non Finnish (NFE) AF: 0.470 AC: 482754 AN: 1027432

Other (OTH) AF: 0.472 AC: 26155 AN: 55444

GnomAD4 genome AF: 0.504 AC: 76458 AN: 151728 Hom.: 19826 Cov.: 32 AF XY: 0.503 AC XY: 37295 AN XY: 74132

African (AFR) AF: 0.619 AC: 25651 AN: 41424

American (AMR) AF: 0.473 AC: 7175 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1846 AN: 5146

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4822

European-Finnish (FIN) AF: 0.556 AC: 5856 AN: 10538

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31277 AN: 67836

Other (OTH) AF: 0.472 AC: 993 AN: 2106

Alfa AF: 0.488 Hom.: 5137

Bravo AF: 0.505

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.39
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6447493; hg19: chr4-46042945; COSMIC: COSV54951607;