4-46053606-G-T

Variant names:

• chr4-46053606-G-T
• rs13140445
• NM_173536.4:c.917-1968C>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.917-1968C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,724 control chromosomes in the GnomAD database, including 5,144 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 0.23 (5144 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.917-1968C>A		intron_variant	Intron 7 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.530-1968C>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.917-1968C>A		intron_variant	Intron 7 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34661 AN: 151606 Hom.: 5151 Cov.: 31

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.228 AC: 34655 AN: 151724 Hom.: 5144 Cov.: 31 AF XY: 0.224 AC XY: 16596 AN XY: 74146

African (AFR) AF: 0.0587 AC: 2433 AN: 41420

American (AMR) AF: 0.223 AC: 3376 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1150 AN: 3462

East Asian (EAS) AF: 0.0223 AC: 115 AN: 5166

South Asian (SAS) AF: 0.168 AC: 809 AN: 4828

European-Finnish (FIN) AF: 0.312 AC: 3273 AN: 10498

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22464 AN: 67878

Other (OTH) AF: 0.251 AC: 527 AN: 2098

Alfa AF: 0.152 Hom.: 338

Bravo AF: 0.216

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.048
DANN	Benign	0.40
PhyloP100		-1.7
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: rs13140445; hg19: chr4-46055623;