4-46053461-C-T

Variant names:

• chr4-46053461-C-T
• rs993677
• NM_173536.4:c.917-1823G>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.917-1823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 151,962 control chromosomes in the GnomAD database, including 62,181 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 0.90 (62181 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.917-1823G>A		intron_variant	Intron 7 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.530-1823G>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.917-1823G>A		intron_variant	Intron 7 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137134 AN: 151844 Hom.: 62129 Cov.: 32

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.903 AC: 137246 AN: 151962 Hom.: 62181 Cov.: 32 AF XY: 0.904 AC XY: 67150 AN XY: 74264

African (AFR) AF: 0.977 AC: 40559 AN: 41522

American (AMR) AF: 0.876 AC: 13290 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3295 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4319 AN: 5152

South Asian (SAS) AF: 0.933 AC: 4506 AN: 4830

European-Finnish (FIN) AF: 0.903 AC: 9558 AN: 10584

Middle Eastern (MID) AF: 0.945 AC: 276 AN: 292

European-Non Finnish (NFE) AF: 0.865 AC: 58750 AN: 67914

Other (OTH) AF: 0.899 AC: 1897 AN: 2110

Alfa AF: 0.876 Hom.: 75130

Bravo AF: 0.904

Asia WGS AF: 0.903 AC: 3137 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.53
DANN	Benign	0.22
PhyloP100		-0.66
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: rs993677; hg19: chr4-46055478;