ENST00000685980.2:n.*1607-567G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000685980.2(KCNA3):​n.*1607-567G>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 ENST00000685980.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 4 publications found

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]

ENSG00000300042 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000685980.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNA3	NR_109845.2		n.219-567G>A		intron	N/A
	KCNA3	NR_109846.1		n.301-570G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNA3	ENST00000685980.2		n.*1607-567G>A		intron	N/A	ENSP00000513296.1
	KCNA3	ENST00000697409.1		n.*1607-570G>A		intron	N/A	ENSP00000513297.1
	KCNA3	ENST00000697410.1		n.*1667-567G>A		intron	N/A	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

African (AFR) AF: 0.659 AC: 27354 AN: 41484

American (AMR) AF: 0.643 AC: 9820 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2558 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2869 AN: 5174

South Asian (SAS) AF: 0.565 AC: 2727 AN: 4828

European-Finnish (FIN) AF: 0.664 AC: 7016 AN: 10572

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47168 AN: 67982

Other (OTH) AF: 0.685 AC: 1444 AN: 2108

Alfa AF: 0.689 Hom.: 53002

Bravo AF: 0.667

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		0.26

Splicing

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

Other links and lift over

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