rs2162241

chr15-26731635-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+40767A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,000 control chromosomes in the GnomAD database, including 30,422 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 0.63 (30422 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.240+40767A>G		intron_variant		ENST00000311550.10
GABRB3	NM_001278631.2	c.-112+40767A>G		intron_variant
GABRB3	NM_021912.5	c.240+40767A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+40767A>G		intron_variant		1	NM_000814.6	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95458 AN: 151882 Hom.: 30398 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.628 AC: 95529 AN: 152000 Hom.: 30422 Cov.: 32 AF XY: 0.630 AC XY: 46786 AN XY: 74266

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.632

Alfa AF: 0.618 Hom.: 6616

Bravo AF: 0.639

Asia WGS AF: 0.825 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.45
Dann	Benign	0.53

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: rs2162241; hg19: chr15-26976782;