rs1391168

Variant names:

• chr4-46113142-G-A
• rs1391168
• NM_173536.4:c.104+10668C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-46113142-G-A
• chr4-46113142-G-C
• chr4-46113142-G-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.104+10668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 150,746 control chromosomes in the GnomAD database, including 24,949 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 0.56 (24949 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 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.104+10668C>T		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.104+10668C>T		intron	N/A	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84157 AN: 150626 Hom.: 24904 Cov.: 31

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.559 AC: 84259 AN: 150746 Hom.: 24949 Cov.: 31 AF XY: 0.550 AC XY: 40471 AN XY: 73620

African (AFR) AF: 0.753 AC: 31078 AN: 41292

American (AMR) AF: 0.472 AC: 7089 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1310 AN: 3440

East Asian (EAS) AF: 0.361 AC: 1835 AN: 5088

South Asian (SAS) AF: 0.317 AC: 1523 AN: 4802

European-Finnish (FIN) AF: 0.494 AC: 5202 AN: 10538

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

European-Non Finnish (NFE) AF: 0.514 AC: 34600 AN: 67264

Other (OTH) AF: 0.519 AC: 1085 AN: 2090

Alfa AF: 0.496 Hom.: 14395

Bravo AF: 0.569

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		-0.23
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: rs1391168; hg19: chr4-46115159;