rs2640480

Positions:

• chr1-110670626-C-A
• chr1-110670626-C-G
• chr1-110670626-C-T

Variant summary

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

The ENST00000685980.2(KCNA3):​c.*1606+850G>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,930 control chromosomes in the GnomAD database, including 34,587 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 (34587 hom., cov: 32)
• Consequence: KCNA3 ENST00000685980.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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=-0.85).
• 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/exons	MANE	UniProt
KCNA3	NR_109845.2	n.219-2282G>T		intron_variant, non_coding_transcript_variant
KCNA3	NR_109846.1	n.300+850G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA3	ENST00000685980.2	c.*1606+850G>T		intron_variant, NMD_transcript_variant
KCNA3	ENST00000697409.1	c.*1606+850G>T		intron_variant, NMD_transcript_variant
KCNA3	ENST00000697410.1	c.*1607-797G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102377 AN: 151812 Hom.: 34561 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.674 AC: 102456 AN: 151930 Hom.: 34587 Cov.: 32 AF XY: 0.668 AC XY: 49581 AN XY: 74238

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.686

Alfa AF: 0.692 Hom.: 37946

Bravo AF: 0.673

Asia WGS AF: 0.567 AC: 1971 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2640480; hg19: chr1-111213248;