2-223072841-T-G

Variant names:

• chr2-223072841-T-G
• rs960246
• ENST00000488477.2:n.189+12138T>G

Variant summary

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

The ENST00000488477.2(KCNE4):​n.189+12138T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,212 control chromosomes in the GnomAD database, including 61,351 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 0.90 (61351 hom., cov: 32)
• Consequence: KCNE4 ENST00000488477.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124907986	XR_007088096.1	n.109+12138T>G		intron_variant	Intron 1 of 1
LOC124907986	XR_007088097.1	n.110-3646T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000488477.2	n.189+12138T>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136433 AN: 152094 Hom.: 61309 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.897 AC: 136531 AN: 152212 Hom.: 61351 Cov.: 32 AF XY: 0.899 AC XY: 66907 AN XY: 74414

African (AFR) AF: 0.910 AC: 37791 AN: 41522

American (AMR) AF: 0.888 AC: 13578 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2570 AN: 3470

East Asian (EAS) AF: 0.975 AC: 5053 AN: 5182

South Asian (SAS) AF: 0.910 AC: 4382 AN: 4816

European-Finnish (FIN) AF: 0.938 AC: 9954 AN: 10610

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.888 AC: 60382 AN: 68014

Other (OTH) AF: 0.860 AC: 1814 AN: 2110

Alfa AF: 0.883 Hom.: 232959

Bravo AF: 0.892

Asia WGS AF: 0.915 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.70
PhyloP100		0.58

Splicing

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

Other links and lift over

dbSNP: rs960246; hg19: chr2-223937559;