rs1497570

Variant names:

• chr4-46045017-C-A
• rs1497570
• NM_173536.4:c.1132-3763G>T

Variant summary

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

The NM_173536.4(GABRG1):​c.1132-3763G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,900 control chromosomes in the GnomAD database, including 20,011 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 0.51 (20011 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.1132-3763G>T		intron_variant	Intron 8 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.745-3763G>T		intron_variant	Intron 6 of 6		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.1132-3763G>T		intron_variant	Intron 8 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76700 AN: 151784 Hom.: 19975 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.506 AC: 76806 AN: 151900 Hom.: 20011 Cov.: 32 AF XY: 0.505 AC XY: 37448 AN XY: 74214

African (AFR) AF: 0.625 AC: 25918 AN: 41464

American (AMR) AF: 0.472 AC: 7183 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1469 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1845 AN: 5142

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4816

European-Finnish (FIN) AF: 0.556 AC: 5870 AN: 10554

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31328 AN: 67940

Other (OTH) AF: 0.474 AC: 998 AN: 2106

Alfa AF: 0.487 Hom.: 2384

Bravo AF: 0.507

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.61
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: rs1497570; hg19: chr4-46047034;