chr2-223072020-C-T

Variant names:

• chr2-223072020-C-T
• rs1440072
• ENST00000488477.2:n.189+11317C>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+11317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,216 control chromosomes in the GnomAD database, including 67,193 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 0.94 (67193 hom., cov: 32)
• Consequence: KCNE4 ENST00000488477.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 19 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124907986	XR_007088096.1	n.109+11317C>T		intron_variant	Intron 1 of 1
LOC124907986	XR_007088097.1	n.110-4467C>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+11317C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142818 AN: 152098 Hom.: 67135 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.939 AC: 142935 AN: 152216 Hom.: 67193 Cov.: 32 AF XY: 0.939 AC XY: 69898 AN XY: 74426

African (AFR) AF: 0.953 AC: 39563 AN: 41524

American (AMR) AF: 0.926 AC: 14152 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2897 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5090 AN: 5184

South Asian (SAS) AF: 0.917 AC: 4416 AN: 4816

European-Finnish (FIN) AF: 0.966 AC: 10254 AN: 10610

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63584 AN: 68008

Other (OTH) AF: 0.913 AC: 1931 AN: 2116

Alfa AF: 0.932 Hom.: 226516

Bravo AF: 0.936

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.055
DANN	Benign	0.61
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs1440072; hg19: chr2-223936738;