rs3762611

Variant names:

• chr4-46995271-G-A
• rs3762611
• ENST00000513567.5:c.-20+1345G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513567.5(GABRB1):​c.-20+1345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,220 control chromosomes in the GnomAD database, including 732 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 0.092 (732 hom., cov: 32)
• Consequence: GABRB1 ENST00000513567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 11 publications found

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]

GABRB1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 45

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000513567.5	TSL:4	c.-20+1345G>A		intron	N/A	ENSP00000426753.1	D6REM0

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13968 AN: 152102 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0775

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.0919 AC: 13991 AN: 152220 Hom.: 732 Cov.: 32 AF XY: 0.0932 AC XY: 6939 AN XY: 74428

African (AFR) AF: 0.117 AC: 4847 AN: 41548

American (AMR) AF: 0.0774 AC: 1183 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3468

East Asian (EAS) AF: 0.0997 AC: 517 AN: 5186

South Asian (SAS) AF: 0.189 AC: 910 AN: 4816

European-Finnish (FIN) AF: 0.0822 AC: 871 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5097 AN: 68008

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0864 Hom.: 341

Bravo AF: 0.0882

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.90
DANN	Benign	0.50
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs3762611; hg19: chr4-46997288;