rs3212331

chr15-26769622-C-T

Variant summary

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

The NM_000814.6(GABRB3):c.240+2780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,078 control chromosomes in the GnomAD database, including 39,062 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 0.72 (39062 hom., cov: 31)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

LOC112268151 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.240+2780G>A		intron_variant		ENST00000311550.10
LOC112268151	XR_002957720.2	n.2501G>A		non_coding_transcript_exon_variant	1/2
GABRB3	NM_001278631.2	c.-112+2780G>A		intron_variant
GABRB3	NM_021912.5	c.240+2780G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+2780G>A		intron_variant		1	NM_000814.6	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108738 AN: 151960 Hom.: 39025 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.716 AC: 108825 AN: 152078 Hom.: 39062 Cov.: 31 AF XY: 0.712 AC XY: 52951 AN XY: 74330

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.711

Alfa AF: 0.726 Hom.: 5895

Bravo AF: 0.704

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.4
Dann	Benign	0.83

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: rs3212331; hg19: chr15-27014769;