rs1497577

Positions:

• chr4-46091696-T-A
• chr4-46091696-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173536.4(GABRG1):​c.253+5505A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,730 control chromosomes in the GnomAD database, including 16,427 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 0.46 (16427 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG1	NM_173536.4	c.253+5505A>T		intron_variant		ENST00000295452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG1	ENST00000295452.5	c.253+5505A>T		intron_variant		1	NM_173536.4	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69894 AN: 151614 Hom.: 16415 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.461 AC: 69951 AN: 151730 Hom.: 16427 Cov.: 31 AF XY: 0.456 AC XY: 33823 AN XY: 74096

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.450

Alfa AF: 0.325 Hom.: 809

Bravo AF: 0.460

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
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: rs1497577; hg19: chr4-46093713;