rs1597167

Positions:

• chr2-223179532-A-G
• chr2-223179532-A-T

Variant summary

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

The ENST00000488477.2(KCNE4):​n.190-13537A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,034 control chromosomes in the GnomAD database, including 34,641 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 (34641 hom., cov: 31)
• Consequence: KCNE4 ENST00000488477.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718

Genes affected

KCNE4 (HGNC:6244): (potassium voltage-gated channel subfamily E regulatory subunit 4) 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. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the embryo and in adult uterus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000488477.2	n.190-13537A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101261 AN: 151916 Hom.: 34602 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.667 AC: 101346 AN: 152034 Hom.: 34641 Cov.: 31 AF XY: 0.661 AC XY: 49140 AN XY: 74332

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.632

Alfa AF: 0.616 Hom.: 59106

Bravo AF: 0.671

Asia WGS AF: 0.594 AC: 2063 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
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: rs1597167; hg19: chr2-224044250;