rs17536211

chr4-46085716-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GABRG1	NM_173536.4	c.254-1663T>G		intron_variant		ENST00000295452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG1	ENST00000295452.5	c.254-1663T>G		intron_variant		1	NM_173536.4	P1

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

Gnomad4 AFR AF: 0.0350

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.153

Alfa AF: 0.163 Hom.: 298

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17536211; hg19: chr4-46087733;