rs1497577

Variant names:

• chr4-46091696-T-A
• rs1497577
• NM_173536.4:c.253+5505A>T

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 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.253+5505A>T		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.253+5505A>T		intron	N/A	ENSP00000295452.4	Q8N1C3
	GABRG1	ENST00000964875.1		c.253+5505A>T		intron	N/A	ENSP00000634934.1

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

African (AFR) AF: 0.437 AC: 18085 AN: 41384

American (AMR) AF: 0.435 AC: 6624 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1864 AN: 5112

South Asian (SAS) AF: 0.315 AC: 1515 AN: 4806

European-Finnish (FIN) AF: 0.495 AC: 5211 AN: 10526

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33835 AN: 67898

Other (OTH) AF: 0.450 AC: 946 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.67
PhyloP100		1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1497577;

hg19: chr4-46093713;