rs3762607

chr4-46994321-A-G

Variant summary

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

The ENST00000513567.5(GABRB1):c.-20+395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 151,946 control chromosomes in the GnomAD database, including 637 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 0.085 (637 hom., cov: 31)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: GABRB1 ENST00000513567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	XM_024453976.2	c.-20+361A>G		intron_variant
GABRB1	XM_024453977.2	c.-57-56A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000513567.5	c.-20+395A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12948 AN: 151750 Hom.: 636 Cov.: 31

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0815

GnomAD4 exome AF: 0.0256 AC: 2 AN: 78 Hom.: 0 Cov.: 0 AF XY: 0.0185 AC XY: 1 AN XY: 54

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0370

GnomAD4 genome AF: 0.0854 AC: 12967 AN: 151868 Hom.: 637 Cov.: 31 AF XY: 0.0871 AC XY: 6466 AN XY: 74230

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.0733

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0838

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0856 Hom.: 124

Bravo AF: 0.0806

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.4
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: rs3762607; hg19: chr4-46996338;