rs6287

Positions:

• chr4-47406648-A-G

Variant summary

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

The ENST00000295454.8(GABRB1):​c.836-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,611,570 control chromosomes in the GnomAD database, including 11,854 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 0.12 (1094 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10760 hom.)
• Consequence: GABRB1 ENST00000295454.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.836-34A>G		intron_variant		ENST00000295454.8	NP_000803.2
GABRB1	XM_017007985.2	c.185-34A>G		intron_variant			XP_016863474.1
GABRB1	XM_024453976.2	c.737-34A>G		intron_variant			XP_024309744.1
GABRB1	XM_024453977.2	c.737-34A>G		intron_variant			XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.836-34A>G		intron_variant		1	NM_000812.4	ENSP00000295454	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17645 AN: 152130 Hom.: 1095 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.105 AC: 26147 AN: 249870 Hom.: 1558 AF XY: 0.105 AC XY: 14227 AN XY: 135174

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.0700

Gnomad ASJ exome AF: 0.0913

Gnomad EAS exome AF: 0.00288

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.118 AC: 171912 AN: 1459322 Hom.: 10760 Cov.: 31 AF XY: 0.118 AC XY: 85334 AN XY: 725702

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0726

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.00502

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.116 AC: 17649 AN: 152248 Hom.: 1094 Cov.: 32 AF XY: 0.113 AC XY: 8418 AN XY: 74444

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0901

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.111

Alfa AF: 0.118 Hom.: 273

Bravo AF: 0.113

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.57

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: rs6287; hg19: chr4-47408665;