chr4-46103850-T-A

Variant names:

• chr4-46103850-T-A
• rs1391166
• NM_173536.4:c.105-6501A>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.105-6501A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 150,948 control chromosomes in the GnomAD database, including 27,690 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 0.59 (27690 hom., cov: 30)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.105-6501A>T		intron_variant	Intron 1 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.105-6501A>T		intron_variant	Intron 1 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89381 AN: 150830 Hom.: 27644 Cov.: 30

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.593 AC: 89486 AN: 150948 Hom.: 27690 Cov.: 30 AF XY: 0.588 AC XY: 43331 AN XY: 73664

African (AFR) AF: 0.759 AC: 31381 AN: 41326

American (AMR) AF: 0.544 AC: 8204 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1464 AN: 3454

East Asian (EAS) AF: 0.364 AC: 1850 AN: 5086

South Asian (SAS) AF: 0.352 AC: 1692 AN: 4810

European-Finnish (FIN) AF: 0.611 AC: 6409 AN: 10494

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

European-Non Finnish (NFE) AF: 0.546 AC: 36797 AN: 67396

Other (OTH) AF: 0.548 AC: 1149 AN: 2096

Alfa AF: 0.576 Hom.: 3242

Bravo AF: 0.596

Asia WGS AF: 0.395 AC: 1362 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	9.4
DANN	Benign	0.79
PhyloP100		-0.022
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: rs1391166; hg19: chr4-46105867;