rs6576618

chr15-26799458-A-Cchr15-26799458-A-Gchr15-26799458-A-T

Variant summary

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

The ENST00000541819.6(GABRB3):c.248+16909T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 150,926 control chromosomes in the GnomAD database, including 27,564 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 0.60 (27564 hom., cov: 28)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000541819.6	c.248+16909T>G		intron_variant		1
GABRB3	ENST00000637226.1	n.13-3366T>G		intron_variant, non_coding_transcript_variant		5
GABRB3	ENST00000637893.1	n.41-1012T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90275 AN: 150828 Hom.: 27544 Cov.: 28

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.598 AC: 90321 AN: 150926 Hom.: 27564 Cov.: 28 AF XY: 0.605 AC XY: 44576 AN XY: 73674

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.610

Alfa AF: 0.543 Hom.: 3635

Bravo AF: 0.605

Asia WGS AF: 0.795 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.85
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: rs6576618; hg19: chr15-27044605;