15-26547268-C-T

Position:

• chr15-26547268-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.*525G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 350,814 control chromosomes in the GnomAD database, including 8,787 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 0.21 (3553 hom., cov: 32)
  • Exomes 𝑓: 0.22 (5234 hom.)
• Consequence: GABRB3 NM_000814.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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]

GABRB3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.*525G>A		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	c.*525G>A		3_prime_UTR_variant	9/9	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31783 AN: 151922 Hom.: 3551 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0783

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.218 AC: 43316 AN: 198774 Hom.: 5234 Cov.: 0 AF XY: 0.218 AC XY: 22011 AN XY: 100790

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.0486

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.209 AC: 31803 AN: 152040 Hom.: 3553 Cov.: 32 AF XY: 0.209 AC XY: 15506 AN XY: 74282

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0781

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.190

Alfa AF: 0.219 Hom.: 3826

Bravo AF: 0.207

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.75

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: rs11637141; hg19: chr15-26792415;