rs12720447

Variant names:

• chr2-223052899-C-T
• rs12720447
• NM_080671.4:c.69C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_080671.4(KCNE4):​c.69C>T​(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,998 control chromosomes in the GnomAD database, including 549 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 0.036 (243 hom., cov: 33)
  • Exomes 𝑓: 0.011 (306 hom.)
• Consequence: KCNE4 NM_080671.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832
• 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.832 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	NM_080671.4	MANE Select	c.69C>T	p.Ser23Ser	synonymous	Exon 2 of 2	NP_542402.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	ENST00000281830.4	TSL:1 MANE Select	c.69C>T	p.Ser23Ser	synonymous	Exon 2 of 2	ENSP00000281830.5
	KCNE4	ENST00000488477.2	TSL:3	n.75+625C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5437 AN: 152206 Hom.: 243 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0194 AC: 4851 AN: 250504 AF XY: 0.0173

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0361

Gnomad ASJ exome AF: 0.000697

Gnomad EAS exome AF: 0.00941

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.00525

Gnomad OTH exome AF: 0.0142

GnomAD4 exome AF: 0.0110 AC: 16141 AN: 1461674 Hom.: 306 Cov.: 31 AF XY: 0.0111 AC XY: 8049 AN XY: 727154

African (AFR) AF: 0.103 AC: 3454 AN: 33476

American (AMR) AF: 0.0352 AC: 1574 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000804 AC: 21 AN: 26126

East Asian (EAS) AF: 0.00897 AC: 356 AN: 39696

South Asian (SAS) AF: 0.0291 AC: 2509 AN: 86250

European-Finnish (FIN) AF: 0.00353 AC: 188 AN: 53314

Middle Eastern (MID) AF: 0.00832 AC: 48 AN: 5768

European-Non Finnish (NFE) AF: 0.00642 AC: 7140 AN: 1111936

Other (OTH) AF: 0.0141 AC: 851 AN: 60384

GnomAD4 genome AF: 0.0358 AC: 5448 AN: 152324 Hom.: 243 Cov.: 33 AF XY: 0.0344 AC XY: 2563 AN XY: 74470

African (AFR) AF: 0.104 AC: 4327 AN: 41570

American (AMR) AF: 0.0283 AC: 434 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5174

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4826

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00579 AC: 394 AN: 68032

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0190 Hom.: 67

Bravo AF: 0.0410

Asia WGS AF: 0.0290 AC: 102 AN: 3478

EpiCase AF: 0.00649

EpiControl AF: 0.00664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs12720447; hg19: chr2-223917617;