rs1892593

Positions:

• chr21-34454062-G-A
• chr21-34454062-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000219.6(KCNE1):​c.-50-4378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.44 (10983 hom., cov: 11)
  • Failed GnomAD Quality Control
• Consequence: KCNE1 NM_000219.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.-50-4378C>T		intron_variant		ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3	c.-50-4378C>T		intron_variant		1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 37495 AN: 85144 Hom.: 10975 Cov.: 11 FAILED QC

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.464

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.448

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.440 AC: 37525 AN: 85248 Hom.: 10983 Cov.: 11 AF XY: 0.440 AC XY: 17760 AN XY: 40330

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.448

Alfa AF: 0.333 Hom.: 11859

Asia WGS AF: 0.436 AC: 1519 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	1.1
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1892593; hg19: chr21-35826360;