15-26747019-T-C

Position:

• chr15-26747019-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000814.6(GABRB3):​c.240+25383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 86,146 control chromosomes in the GnomAD database, including 1 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 0.00057 (1 hom., cov: 23)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.99

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BS2: High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.240+25383A>G		intron_variant		ENST00000311550.10	NP_000805.1
GABRB3	NM_021912.5	c.240+25383A>G		intron_variant			NP_068712.1
GABRB3	NM_001278631.2	c.-112+25383A>G		intron_variant			NP_001265560.1
LOC112268151	XR_002957720.2	n.7931A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+25383A>G		intron_variant		1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 48 AN: 86064 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000959

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000758

Gnomad SAS AF: 0.00737

Gnomad FIN AF: 0.000437

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.000805

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

GnomAD4 genome AF: 0.000569 AC: 49 AN: 86146 Hom.: 1 Cov.: 23 AF XY: 0.000762 AC XY: 32 AN XY: 42018

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000957

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000759

Gnomad4 SAS AF: 0.00775

Gnomad4 FIN AF: 0.000437

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.000795

Alfa AF: 0.0153 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0020
DANN	Benign	0.30

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: rs12905535; hg19: chr15-26992166;