chr4-46995271-G-A

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	XM_024453976.2	c.-20+1311G>A		intron_variant	Intron 1 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.-20+857G>A		intron_variant	Intron 2 of 9		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000513567.5	c.-20+1345G>A		intron_variant	Intron 1 of 3	4		ENSP00000426753.1

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 v4.3

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;