rs4273008

Positions:

• chr15-26775161-A-C

Variant summary

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

The ENST00000541819.6(GABRB3):​c.249-2389T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,296 control chromosomes in the GnomAD database, including 63,421 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 0.91 (63421 hom., cov: 33)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

Genes affected

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

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 (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000541819.6	c.249-2389T>G		intron_variant		1		ENSP00000442408
GABRB3	ENST00000557641.5	n.453-2389T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138700 AN: 152178 Hom.: 63379 Cov.: 33

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.911 AC: 138800 AN: 152296 Hom.: 63421 Cov.: 33 AF XY: 0.914 AC XY: 68027 AN XY: 74466

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.983

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.913

Alfa AF: 0.912 Hom.: 8170

Bravo AF: 0.906

Asia WGS AF: 0.976 AC: 3396 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	2.7
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4273008; hg19: chr15-27020308;