rs11701049

Positions:

• chr21-34495846-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KCNE1	NM_000219.6	c.-162+15255A>G		intron_variant		ENST00000399286.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNE1	ENST00000399286.3	c.-162+15255A>G		intron_variant		1	NM_000219.6	P1

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

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.00462

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0538 Hom.: 67

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

Splicing

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

Publications

LitVar

Other links and lift over

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