chr15-26704940-T-C

Position:

• chr15-26704940-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+67462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,042 control chromosomes in the GnomAD database, including 24,685 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 0.55 (24685 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.240+67462A>G		intron_variant		ENST00000311550.10	NP_000805.1
GABRB3	NM_001191320.2	c.-16+11674A>G		intron_variant			NP_001178249.1
GABRB3	NM_001278631.2	c.-111-62412A>G		intron_variant			NP_001265560.1
GABRB3	NM_021912.5	c.240+67462A>G		intron_variant			NP_068712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+67462A>G		intron_variant		1	NM_000814.6	ENSP00000308725	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84336 AN: 151924 Hom.: 24683 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.555 AC: 84365 AN: 152042 Hom.: 24685 Cov.: 32 AF XY: 0.561 AC XY: 41743 AN XY: 74356

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.561

Alfa AF: 0.498 Hom.: 2150

Bravo AF: 0.537

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.40

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: rs7181473; hg19: chr15-26950087;