rs1391168

Positions:

• chr4-46113142-G-A
• chr4-46113142-G-C
• chr4-46113142-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.104+10668C>T		intron_variant		ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.104+10668C>T		intron_variant		1	NM_173536.4	ENSP00000295452	P1

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

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.519

Alfa AF: 0.490 Hom.: 10084

Bravo AF: 0.569

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1391168; hg19: chr4-46115159;