4-46085255-T-G

Variant names:

• chr4-46085255-T-G
• rs1826923
• NM_173536.4:c.254-1202A>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.254-1202A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,024 control chromosomes in the GnomAD database, including 26,418 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 0.58 (26418 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	NM_173536.4	MANE Select	c.254-1202A>C		intron	N/A	NP_775807.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG1	ENST00000295452.5	TSL:1 MANE Select	c.254-1202A>C		intron	N/A	ENSP00000295452.4
	GABRG1	ENST00000964875.1		c.254-1202A>C		intron	N/A	ENSP00000634934.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 87988 AN: 150904 Hom.: 26374 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.583 AC: 88102 AN: 151024 Hom.: 26418 Cov.: 31 AF XY: 0.580 AC XY: 42749 AN XY: 73752

African (AFR) AF: 0.692 AC: 28612 AN: 41350

American (AMR) AF: 0.547 AC: 8240 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1470 AN: 3458

East Asian (EAS) AF: 0.358 AC: 1829 AN: 5108

South Asian (SAS) AF: 0.337 AC: 1620 AN: 4814

European-Finnish (FIN) AF: 0.641 AC: 6756 AN: 10542

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 37724 AN: 67382

Other (OTH) AF: 0.544 AC: 1140 AN: 2094

Alfa AF: 0.469 Hom.: 1404

Bravo AF: 0.584

Asia WGS AF: 0.395 AC: 1372 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.14
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: rs1826923; hg19: chr4-46087272;