rs10032631

Variant names:

• chr4-46047103-G-A
• rs10032631
• NM_173536.4:c.1131+4321C>T

Variant summary

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

The NM_173536.4(GABRG1):​c.1131+4321C>T 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 151,984 control chromosomes in the GnomAD database, including 20,052 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 (20052 hom., cov: 33)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 3 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 = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.1131+4321C>T		intron_variant	Intron 8 of 8	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.744+4321C>T		intron_variant	Intron 6 of 6		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.1131+4321C>T		intron_variant	Intron 8 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76810 AN: 151866 Hom.: 20016 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.506 AC: 76916 AN: 151984 Hom.: 20052 Cov.: 33 AF XY: 0.505 AC XY: 37514 AN XY: 74252

African (AFR) AF: 0.626 AC: 25955 AN: 41482

American (AMR) AF: 0.473 AC: 7213 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1850 AN: 5134

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4826

European-Finnish (FIN) AF: 0.559 AC: 5902 AN: 10566

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

European-Non Finnish (NFE) AF: 0.461 AC: 31347 AN: 67956

Other (OTH) AF: 0.473 AC: 998 AN: 2110

Alfa AF: 0.487 Hom.: 3070

Bravo AF: 0.507

Asia WGS AF: 0.395 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.54
PhyloP100		-0.28
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: rs10032631; hg19: chr4-46049120;