rs737098

chr15-26722023-A-Gchr15-26722023-A-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+50379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,076 control chromosomes in the GnomAD database, including 4,423 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 0.24 (4423 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.240+50379T>C		intron_variant		ENST00000311550.10
GABRB3	NM_001278631.2	c.-112+50379T>C		intron_variant
GABRB3	NM_021912.5	c.240+50379T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+50379T>C		intron_variant		1	NM_000814.6	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35831 AN: 151956 Hom.: 4417 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.236 AC: 35852 AN: 152076 Hom.: 4423 Cov.: 32 AF XY: 0.236 AC XY: 17551 AN XY: 74338

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.216

Alfa AF: 0.253 Hom.: 2385

Bravo AF: 0.219

Asia WGS AF: 0.143 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.24
Dann	Benign	0.71

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: rs737098; hg19: chr15-26967170;