2-223053645-T-G

Variant names:

• chr2-223053645-T-G
• rs3795884
• NM_080671.4:c.*302T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080671.4(KCNE4):​c.*302T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNE4 NM_080671.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE4	NM_080671.4	c.*302T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000281830.4	NP_542402.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000281830.4	c.*302T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_080671.4	ENSP00000281830.5
KCNE4	ENST00000488477.2	n.75+1371T>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 274298 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 142552

African (AFR) AF: 0.00 AC: 0 AN: 8648

American (AMR) AF: 0.00 AC: 0 AN: 12894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8136

East Asian (EAS) AF: 0.00 AC: 0 AN: 16426

South Asian (SAS) AF: 0.00 AC: 0 AN: 31776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 152842

Other (OTH) AF: 0.00 AC: 0 AN: 15258

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.50
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3795884; hg19: chr2-223918363;