chr4-46084931-T-C

Variant names:

• chr4-46084931-T-C
• rs13130508
• NM_173536.4:c.254-878A>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.254-878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 151,668 control chromosomes in the GnomAD database, including 211 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 0.041 (211 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173536.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	NM_173536.4	MANE Select	c.254-878A>G		intron	N/A	NP_775807.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	ENST00000295452.5	TSL:1 MANE Select	c.254-878A>G		intron	N/A	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6267 AN: 151550 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0336

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

GnomAD4 genome AF: 0.0414 AC: 6281 AN: 151668 Hom.: 211 Cov.: 32 AF XY: 0.0446 AC XY: 3302 AN XY: 74118

African (AFR) AF: 0.0675 AC: 2803 AN: 41502

American (AMR) AF: 0.0768 AC: 1164 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3464

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5142

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4826

European-Finnish (FIN) AF: 0.0730 AC: 773 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0200 AC: 1356 AN: 67674

Other (OTH) AF: 0.0332 AC: 70 AN: 2108

Alfa AF: 0.0355 Hom.: 13

Bravo AF: 0.0417

Asia WGS AF: 0.0160 AC: 56 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		2.0
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: rs13130508; hg19: chr4-46086948;