rs17536211

Variant names:

• chr4-46085716-A-C
• rs17536211
• NM_173536.4:c.254-1663T>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.254-1663T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,482 control chromosomes in the GnomAD database, including 1,933 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 0.14 (1933 hom., cov: 32)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.254-1663T>G		intron_variant	Intron 2 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.254-1663T>G		intron_variant	Intron 2 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21052 AN: 151364 Hom.: 1937 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.139 AC: 21043 AN: 151482 Hom.: 1933 Cov.: 32 AF XY: 0.136 AC XY: 10080 AN XY: 74012

African (AFR) AF: 0.0350 AC: 1453 AN: 41506

American (AMR) AF: 0.132 AC: 2002 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 844 AN: 3464

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5150

South Asian (SAS) AF: 0.0530 AC: 256 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2263 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13639 AN: 67498

Other (OTH) AF: 0.153 AC: 321 AN: 2102

Alfa AF: 0.153 Hom.: 317

Bravo AF: 0.130

Asia WGS AF: 0.0290 AC: 101 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		0.54
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: rs17536211; hg19: chr4-46087733;