rs1497575

Variant names:

• chr4-46091334-G-A
• rs1497575
• NM_173536.4:c.253+5867C>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.253+5867C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,854 control chromosomes in the GnomAD database, including 30,135 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 0.61 (30135 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.253+5867C>T		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.253+5867C>T		intron_variant	Intron 2 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92660 AN: 151736 Hom.: 30085 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.611 AC: 92771 AN: 151854 Hom.: 30135 Cov.: 31 AF XY: 0.606 AC XY: 44948 AN XY: 74162

African (AFR) AF: 0.835 AC: 34656 AN: 41496

American (AMR) AF: 0.549 AC: 8360 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1875 AN: 5110

South Asian (SAS) AF: 0.349 AC: 1683 AN: 4822

European-Finnish (FIN) AF: 0.598 AC: 6300 AN: 10536

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36716 AN: 67900

Other (OTH) AF: 0.558 AC: 1173 AN: 2102

Alfa AF: 0.546 Hom.: 39171

Bravo AF: 0.618

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.67
PhyloP100		-0.41
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: rs1497575; hg19: chr4-46093351;