chr4-46060755-A-C

Variant names:

• chr4-46060755-A-C
• rs1948609
• NM_173536.4:c.626-2133T>G

Variant summary

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

The NM_173536.4(GABRG1):​c.626-2133T>G 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 151,770 control chromosomes in the GnomAD database, including 19,974 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 (19974 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 1 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=-0.87).
• 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.626-2133T>G		intron_variant	Intron 5 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.239-2133T>G		intron_variant	Intron 3 of 6		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.626-2133T>G		intron_variant	Intron 5 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76629 AN: 151652 Hom.: 19938 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.557

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: 76735 AN: 151770 Hom.: 19974 Cov.: 31 AF XY: 0.505 AC XY: 37427 AN XY: 74154

African (AFR) AF: 0.625 AC: 25883 AN: 41404

American (AMR) AF: 0.472 AC: 7185 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1842 AN: 5136

South Asian (SAS) AF: 0.328 AC: 1576 AN: 4802

European-Finnish (FIN) AF: 0.557 AC: 5859 AN: 10526

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

European-Non Finnish (NFE) AF: 0.461 AC: 31319 AN: 67904

Other (OTH) AF: 0.474 AC: 1001 AN: 2112

Alfa AF: 0.388 Hom.: 1570

Bravo AF: 0.507

Asia WGS AF: 0.394 AC: 1370 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.99
DANN	Benign	0.58
PhyloP100		0.017
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: rs1948609; hg19: chr4-46062772;