rs1319782

Variant names:

• chr1-110668911-C-T
• rs1319782
• ENST00000685980.2:n.*1607-567G>A

Variant summary

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

The NR_109845.2(KCNA3):​n.219-567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,110 control chromosomes in the GnomAD database, including 34,051 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 0.67 (34051 hom., cov: 33)
• Consequence: KCNA3 NR_109845.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

Genes affected

KCNA3 (HGNC:6221): (potassium voltage-gated channel subfamily A member 3) Potassium 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, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1. [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 (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA3	NR_109845.2	n.219-567G>A		intron_variant	Intron 1 of 2
KCNA3	NR_109846.1	n.301-570G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNA3	ENST00000685980.2	n.*1607-567G>A		intron_variant	Intron 1 of 2			ENSP00000513296.1
KCNA3	ENST00000697409.1	n.*1607-570G>A		intron_variant	Intron 1 of 2			ENSP00000513297.1
KCNA3	ENST00000697410.1	n.*1667-567G>A		intron_variant	Intron 2 of 3			ENSP00000513298.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101618 AN: 151992 Hom.: 34033 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.668 AC: 101678 AN: 152110 Hom.: 34051 Cov.: 33 AF XY: 0.662 AC XY: 49226 AN XY: 74368

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.685

Alfa AF: 0.695 Hom.: 36776

Bravo AF: 0.667

Asia WGS AF: 0.568 AC: 1976 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	3.8
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1319782; hg19: chr1-111211533; COSMIC: COSV63901962;