rs895767

Positions:

• chr2-223158578-A-C

Variant summary

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

The ENST00000488477.2(KCNE4):​n.190-34491A>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE4	ENST00000488477.2	n.190-34491A>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.176

Alfa AF: 0.148 Hom.: 3958

Bravo AF: 0.168

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs895767; hg19: chr2-224023296;