rs2350439

Variant names:

• chr4-46082400-A-G
• rs2350439
• NM_173536.4:c.321+1586T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-46082400-A-G
• chr4-46082400-A-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.321+1586T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,324 control chromosomes in the GnomAD database, including 20,835 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 0.52 (20835 hom., cov: 30)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.321+1586T>C		intron_variant	Intron 3 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.321+1586T>C		intron_variant	Intron 3 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78668 AN: 151206 Hom.: 20816 Cov.: 30

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.520 AC: 78750 AN: 151324 Hom.: 20835 Cov.: 30 AF XY: 0.514 AC XY: 38039 AN XY: 73960

African (AFR) AF: 0.550 AC: 22726 AN: 41284

American (AMR) AF: 0.462 AC: 6983 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1416 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1832 AN: 5106

South Asian (SAS) AF: 0.325 AC: 1563 AN: 4804

European-Finnish (FIN) AF: 0.567 AC: 5965 AN: 10520

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36514 AN: 67720

Other (OTH) AF: 0.499 AC: 1047 AN: 2100

Alfa AF: 0.527 Hom.: 2760

Bravo AF: 0.519

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.81
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: rs2350439; hg19: chr4-46084417;