NM_000814.6:c.462-9844T>A

Variant names:

• chr15-26593258-A-T
• rs12437672
• NM_000814.6:c.462-9844T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000814.6(GABRB3):​c.462-9844T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,120 control chromosomes in the GnomAD database, including 7,595 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 0.28 (7595 hom., cov: 32)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.462-9844T>A		intron_variant	Intron 4 of 8	ENST00000311550.10	NP_000805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.462-9844T>A		intron_variant	Intron 4 of 8	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42345 AN: 152002 Hom.: 7584 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.279 AC: 42374 AN: 152120 Hom.: 7595 Cov.: 32 AF XY: 0.288 AC XY: 21379 AN XY: 74346

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.258

Alfa AF: 0.282 Hom.: 849

Bravo AF: 0.266

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.58
DANN	Benign	0.67

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: rs12437672; hg19: chr15-26838405;