rs2017247

Positions:

• chr15-26544015-T-C
• chr15-26544015-T-G

Variant summary

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

The NM_000814.6(GABRB3):​c.*3778A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,536 control chromosomes in the GnomAD database, including 46,257 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 0.77 (46164 hom., cov: 32)
  • Exomes 𝑓: 0.70 (93 hom.)
• Consequence: GABRB3 NM_000814.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.*3778A>G		3_prime_UTR_variant	9/9	ENST00000311550.10	NP_000805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.*3778A>G		3_prime_UTR_variant	9/9	1	NM_000814.6	ENSP00000308725	P1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116861 AN: 152016 Hom.: 46117 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.697 AC: 280 AN: 402 Hom.: 93 Cov.: 0 AF XY: 0.702 AC XY: 167 AN XY: 238

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.769 AC: 116965 AN: 152134 Hom.: 46164 Cov.: 32 AF XY: 0.762 AC XY: 56680 AN XY: 74360

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.766

Alfa AF: 0.756 Hom.: 9491

Bravo AF: 0.777

Asia WGS AF: 0.527 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.68

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: rs2017247; hg19: chr15-26789162; COSMIC: COSV54661702; COSMIC: COSV54661702;