rs6813633

Positions:

• chr4-46113962-G-A
• chr4-46113962-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173536.4(GABRG1):​c.104+9848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 150,740 control chromosomes in the GnomAD database, including 24,924 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 (24924 hom., cov: 31)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG1	NM_173536.4	c.104+9848C>T		intron_variant		ENST00000295452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG1	ENST00000295452.5	c.104+9848C>T		intron_variant		1	NM_173536.4	P1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84086 AN: 150622 Hom.: 24879 Cov.: 31

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.558 AC: 84188 AN: 150740 Hom.: 24924 Cov.: 31 AF XY: 0.549 AC XY: 40415 AN XY: 73582

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.517

Alfa AF: 0.538 Hom.: 2953

Bravo AF: 0.569

Asia WGS AF: 0.375 AC: 1304 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.42

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: rs6813633; hg19: chr4-46115979;