rs895767

Variant names:

• chr2-223158578-A-C
• rs895767
• ENST00000488477.2:n.190-34491A>C

Variant summary

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

The ENST00000488477.2(KCNE4):​n.190-34491A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,882 control chromosomes in the GnomAD database, including 2,367 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 0.16 (2367 hom., cov: 32)
• Consequence: KCNE4 ENST00000488477.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488477.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	ENST00000488477.2	TSL:3	n.190-34491A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24843 AN: 151764 Hom.: 2360 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.164 AC: 24878 AN: 151882 Hom.: 2367 Cov.: 32 AF XY: 0.171 AC XY: 12698 AN XY: 74238

African (AFR) AF: 0.128 AC: 5299 AN: 41354

American (AMR) AF: 0.265 AC: 4034 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1816 AN: 5164

South Asian (SAS) AF: 0.244 AC: 1170 AN: 4804

European-Finnish (FIN) AF: 0.223 AC: 2356 AN: 10550

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8887 AN: 67976

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.147 Hom.: 8311

Bravo AF: 0.168

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs895767; hg19: chr2-224023296;