rs4388439

Positions:

• chr8-132196375-A-G

Variant summary

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

The NM_004519.4(KCNQ3):​c.387-10194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,166 control chromosomes in the GnomAD database, including 1,974 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 0.12 (1974 hom., cov: 33)
• Consequence: KCNQ3 NM_004519.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ3	NM_004519.4	c.387-10194T>C		intron_variant		ENST00000388996.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ3	ENST00000388996.10	c.387-10194T>C		intron_variant		1	NM_004519.4	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17854 AN: 152048 Hom.: 1967 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.118 AC: 17887 AN: 152166 Hom.: 1974 Cov.: 33 AF XY: 0.113 AC XY: 8429 AN XY: 74400

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.0614 Hom.: 572

Bravo AF: 0.123

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.090
DANN	Benign	0.41

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: rs4388439; hg19: chr8-133208622;