rs8043440

Positions:

• chr15-26727939-T-C

Variant summary

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

The NM_000814.6(GABRB3):​c.240+44463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,158 control chromosomes in the GnomAD database, including 2,967 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 0.18 (2967 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.240+44463A>G		intron_variant		ENST00000311550.10
GABRB3	NM_001278631.2	c.-112+44463A>G		intron_variant
GABRB3	NM_021912.5	c.240+44463A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+44463A>G		intron_variant		1	NM_000814.6	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27377 AN: 152040 Hom.: 2964 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.180 AC: 27395 AN: 152158 Hom.: 2967 Cov.: 32 AF XY: 0.179 AC XY: 13335 AN XY: 74400

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.164

Alfa AF: 0.139 Hom.: 3406

Bravo AF: 0.190

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8043440; hg19: chr15-26973086;