rs11701049

Variant names:

• chr21-34495846-T-C
• rs11701049
• NM_000219.6:c.-162+15255A>G

Variant summary

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

The NM_000219.6(KCNE1):​c.-162+15255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,148 control chromosomes in the GnomAD database, including 1,787 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 0.14 (1787 hom., cov: 31)
• Consequence: KCNE1 NM_000219.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 1 publications found

Genes affected

KCNE1 (HGNC:6240): (potassium voltage-gated channel subfamily E regulatory subunit 1) The product of this gene belongs to the potassium channel KCNE family. Potassium ion channels are essential to many cellular functions and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. This gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. Mutation in this gene are associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

KCNE1 Gene-Disease associations (from GenCC):

• long QT syndrome 5

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Jervell and Lange-Nielsen syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• atrial fibrillation

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.-162+15255A>G		intron_variant	Intron 2 of 3	ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3	c.-162+15255A>G		intron_variant	Intron 2 of 3	1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21536 AN: 152030 Hom.: 1787 Cov.: 31

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.142 AC: 21535 AN: 152148 Hom.: 1787 Cov.: 31 AF XY: 0.143 AC XY: 10609 AN XY: 74400

African (AFR) AF: 0.0684 AC: 2840 AN: 41530

American (AMR) AF: 0.133 AC: 2030 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3468

East Asian (EAS) AF: 0.00462 AC: 24 AN: 5190

South Asian (SAS) AF: 0.183 AC: 881 AN: 4826

European-Finnish (FIN) AF: 0.183 AC: 1927 AN: 10548

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12750 AN: 67962

Other (OTH) AF: 0.144 AC: 304 AN: 2116

Alfa AF: 0.0607 Hom.: 99

Bravo AF: 0.131

Asia WGS AF: 0.0890 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.5
DANN	Benign	0.83
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11701049; hg19: chr21-35868144; COSMIC: COSV61607228;