2-223094376-C-T

Variant names:

• chr2-223094376-C-T
• rs1448295
• ENST00000488477.2:n.189+33673C>T

Variant summary

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

The ENST00000488477.2(KCNE4):​n.189+33673C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,328 control chromosomes in the GnomAD database, including 64,775 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 0.92 (64775 hom., cov: 35)
• Consequence: KCNE4 ENST00000488477.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 1 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]

LOC124907986 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124907986	XR_007088096.1	n.110-27362C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000488477.2	n.189+33673C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140287 AN: 152210 Hom.: 64730 Cov.: 35

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.922 AC: 140390 AN: 152328 Hom.: 64775 Cov.: 35 AF XY: 0.923 AC XY: 68737 AN XY: 74474

African (AFR) AF: 0.884 AC: 36741 AN: 41568

American (AMR) AF: 0.932 AC: 14265 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5129 AN: 5176

South Asian (SAS) AF: 0.933 AC: 4508 AN: 4830

European-Finnish (FIN) AF: 0.967 AC: 10283 AN: 10630

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63624 AN: 68028

Other (OTH) AF: 0.910 AC: 1923 AN: 2114

Alfa AF: 0.919 Hom.: 10004

Bravo AF: 0.918

Asia WGS AF: 0.947 AC: 3294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.21
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs1448295; hg19: chr2-223959094;