8-132356847-C-G

Position:

• chr8-132356847-C-G

Variant summary

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

The NM_004519.4(KCNQ3):​c.386+123300G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,914 control chromosomes in the GnomAD database, including 19,528 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 0.47 (19528 hom., cov: 32)
• Consequence: KCNQ3 NM_004519.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

Genes affected

KCNQ3 (HGNC:6297): (potassium voltage-gated channel subfamily Q member 3) This gene encodes a protein that functions in the regulation of neuronal excitability. The encoded protein forms an M-channel by associating with the products of the related KCNQ2 or KCNQ5 genes, which both encode integral membrane proteins. M-channel currents are inhibited by M1 muscarinic acetylcholine receptors and are activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

KCNQ3 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ3	NM_004519.4	c.386+123300G>C		intron_variant		ENST00000388996.10	NP_004510.1
KCNQ3	NM_001204824.2	c.26+90354G>C		intron_variant			NP_001191753.1
KCNQ3	XM_047421769.1	c.386+123300G>C		intron_variant			XP_047277725.1
KCNQ3	XM_011517026.3	c.26+73616G>C		intron_variant			XP_011515328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ3	ENST00000388996.10	c.386+123300G>C		intron_variant		1	NM_004519.4	ENSP00000373648.3

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71595 AN: 151798 Hom.: 19507 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.472 AC: 71647 AN: 151914 Hom.: 19528 Cov.: 32 AF XY: 0.469 AC XY: 34822 AN XY: 74220

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.444

Alfa AF: 0.235 Hom.: 492

Bravo AF: 0.493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.69

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: rs978152; hg19: chr8-133369094;