rs2365669

chr1-111820023-G-A

Variant summary

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

The NM_001378969.1(KCND3):c.1107-32917C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,090 control chromosomes in the GnomAD database, including 21,542 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 0.49 (21542 hom., cov: 32)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562

Genes affected

KCND3 (HGNC:6239): (potassium voltage-gated channel subfamily D member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND3	NM_001378969.1	c.1107-32917C>T		intron_variant		ENST00000302127.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND3	ENST00000302127.5	c.1107-32917C>T		intron_variant		5	NM_001378969.1	P3
KCND3	ENST00000315987.6	c.1107-32917C>T		intron_variant		1		P3
KCND3	ENST00000369697.5	c.1107-32917C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74291 AN: 151972 Hom.: 21543 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.488 AC: 74285 AN: 152090 Hom.: 21542 Cov.: 32 AF XY: 0.493 AC XY: 36628 AN XY: 74356

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.525

Alfa AF: 0.601 Hom.: 57714

Bravo AF: 0.462

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.78

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: rs2365669; hg19: chr1-112362645; COSMIC: COSV56177485;