rs2055940

Positions:

• chr4-46995896-G-A
• chr4-46995896-G-T

Variant summary

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

The ENST00000513567.5(GABRB1):​c.-20+1970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,888 control chromosomes in the GnomAD database, including 4,976 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 0.24 (4976 hom., cov: 32)
• Consequence: GABRB1 ENST00000513567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB1	XM_024453976.2	c.-20+1936G>A		intron_variant			XP_024309744.1
GABRB1	XM_024453977.2	c.-20+1482G>A		intron_variant			XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000513567.5	c.-20+1970G>A		intron_variant		4		ENSP00000426753

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35985 AN: 151770 Hom.: 4974 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.237 AC: 35988 AN: 151888 Hom.: 4976 Cov.: 32 AF XY: 0.226 AC XY: 16815 AN XY: 74240

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.271

Alfa AF: 0.301 Hom.: 6382

Bravo AF: 0.239

Asia WGS AF: 0.121 AC: 421 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.99
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2055940; hg19: chr4-46997913;