chr15-26728885-G-A

Variant names:

• chr15-26728885-G-A
• rs1863456
• NM_000814.6:c.240+43517C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000814.6(GABRB3):​c.240+43517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,990 control chromosomes in the GnomAD database, including 16,210 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 0.43 (16210 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.240+43517C>T		intron_variant	Intron 3 of 8	ENST00000311550.10	NP_000805.1
GABRB3	NM_021912.5	c.240+43517C>T		intron_variant	Intron 3 of 8		NP_068712.1
GABRB3	NM_001278631.2	c.-112+43517C>T		intron_variant	Intron 3 of 9		NP_001265560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.240+43517C>T		intron_variant	Intron 3 of 8	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64764 AN: 151872 Hom.: 16196 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.426 AC: 64783 AN: 151990 Hom.: 16210 Cov.: 32 AF XY: 0.431 AC XY: 32052 AN XY: 74294

African (AFR) AF: 0.144 AC: 5972 AN: 41460

American (AMR) AF: 0.593 AC: 9057 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3466

East Asian (EAS) AF: 0.578 AC: 2980 AN: 5152

South Asian (SAS) AF: 0.567 AC: 2735 AN: 4820

European-Finnish (FIN) AF: 0.502 AC: 5302 AN: 10556

Middle Eastern (MID) AF: 0.431 AC: 125 AN: 290

European-Non Finnish (NFE) AF: 0.525 AC: 35645 AN: 67956

Other (OTH) AF: 0.459 AC: 966 AN: 2106

Alfa AF: 0.473 Hom.: 6119

Bravo AF: 0.419

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs1863456; hg19: chr15-26974032;