4-46092242-C-T

Variant names:

• chr4-46092242-C-T
• rs6824361
• NM_173536.4:c.253+4959G>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.253+4959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,672 control chromosomes in the GnomAD database, including 19,327 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 (19327 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.253+4959G>A		intron_variant	Intron 2 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.253+4959G>A		intron_variant	Intron 2 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75862 AN: 151552 Hom.: 19305 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.501 AC: 75938 AN: 151672 Hom.: 19327 Cov.: 32 AF XY: 0.495 AC XY: 36691 AN XY: 74078

African (AFR) AF: 0.526 AC: 21771 AN: 41406

American (AMR) AF: 0.454 AC: 6912 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1885 AN: 5112

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5523 AN: 10502

Middle Eastern (MID) AF: 0.357 AC: 100 AN: 280

European-Non Finnish (NFE) AF: 0.521 AC: 35339 AN: 67838

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.362 Hom.: 938

Bravo AF: 0.501

Asia WGS AF: 0.358 AC: 1232 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		-1.3
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: rs6824361; hg19: chr4-46094259;