rs1373291

Positions:

• chr1-111884229-G-T

Variant summary

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

The NM_001378969.1(KCND3):​c.1107-97123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,100 control chromosomes in the GnomAD database, including 4,874 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 0.25 (4874 hom., cov: 32)
• Consequence: KCND3 NM_001378969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND3	NM_001378969.1	c.1107-97123C>A		intron_variant		ENST00000302127.5	NP_001365898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND3	ENST00000302127.5	c.1107-97123C>A		intron_variant		5	NM_001378969.1	ENSP00000306923	P3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37450 AN: 151980 Hom.: 4864 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.247 AC: 37508 AN: 152100 Hom.: 4874 Cov.: 32 AF XY: 0.253 AC XY: 18800 AN XY: 74338

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.230

Alfa AF: 0.207 Hom.: 4624

Bravo AF: 0.248

Asia WGS AF: 0.392 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.5
DANN	Benign	0.81

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: rs1373291; hg19: chr1-112426851;