rs2221020

Variant names:

• chr4-46101548-C-T
• rs2221020
• NM_173536.4:c.105-4199G>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.105-4199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,388 control chromosomes in the GnomAD database, including 27,231 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 0.59 (27231 hom., cov: 30)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	NM_173536.4	MANE Select	c.105-4199G>A		intron	N/A	NP_775807.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	ENST00000295452.5	TSL:1 MANE Select	c.105-4199G>A		intron	N/A	ENSP00000295452.4	Q8N1C3
	GABRG1	ENST00000964875.1		c.105-4199G>A		intron	N/A	ENSP00000634934.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 88900 AN: 151270 Hom.: 27188 Cov.: 30

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.588 AC: 89002 AN: 151388 Hom.: 27231 Cov.: 30 AF XY: 0.584 AC XY: 43158 AN XY: 73930

African (AFR) AF: 0.743 AC: 30744 AN: 41358

American (AMR) AF: 0.542 AC: 8192 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1460 AN: 3456

East Asian (EAS) AF: 0.364 AC: 1849 AN: 5078

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4814

European-Finnish (FIN) AF: 0.611 AC: 6451 AN: 10560

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 36931 AN: 67692

Other (OTH) AF: 0.548 AC: 1149 AN: 2098

Alfa AF: 0.562 Hom.: 10387

Bravo AF: 0.591

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		0.12
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: rs2221020; hg19: chr4-46103565;