chr4-46057233-C-T

Variant names:

• chr4-46057233-C-T
• rs1497571
• NM_173536.4:c.916+984G>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.916+984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,900 control chromosomes in the GnomAD database, including 19,823 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 (19823 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.916+984G>A		intron_variant	Intron 7 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.529+984G>A		intron_variant	Intron 5 of 6		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.916+984G>A		intron_variant	Intron 7 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76401 AN: 151782 Hom.: 19796 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.504 AC: 76494 AN: 151900 Hom.: 19823 Cov.: 32 AF XY: 0.503 AC XY: 37309 AN XY: 74226

African (AFR) AF: 0.618 AC: 25637 AN: 41468

American (AMR) AF: 0.472 AC: 7186 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1849 AN: 5142

South Asian (SAS) AF: 0.326 AC: 1570 AN: 4820

European-Finnish (FIN) AF: 0.558 AC: 5880 AN: 10546

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

European-Non Finnish (NFE) AF: 0.461 AC: 31311 AN: 67914

Other (OTH) AF: 0.472 AC: 993 AN: 2102

Alfa AF: 0.463 Hom.: 8742

Bravo AF: 0.504

Asia WGS AF: 0.390 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.59
PhyloP100		-1.3
Mutation Taster		=99/1	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: rs1497571; hg19: chr4-46059250;