rs1892593

Variant names:

• chr21-34454062-G-A
• rs1892593
• NM_000219.6:c.-50-4378C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 3 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Jervell and Lange-Nielsen syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000219.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE1	NM_000219.6	MANE Select	c.-50-4378C>T		intron	N/A	NP_000210.2	P15382
	KCNE1	NM_001127668.4		c.-50-4378C>T		intron	N/A	NP_001121140.1	P15382
	KCNE1	NM_001127669.4		c.-50-4378C>T		intron	N/A	NP_001121141.1	C7S316

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.-50-4378C>T		intron	N/A	ENSP00000382226.2	P15382
	KCNE1	ENST00000399289.7	TSL:1	c.-50-4378C>T		intron	N/A	ENSP00000382228.3	P15382
	KCNE1	ENST00000416357.6	TSL:1	c.-51+1324C>T		intron	N/A	ENSP00000416258.2	P15382

Frequencies

GnomAD3 genomes AF: 0.440 AC: 37495 AN: 85144 Hom.: 10975 Cov.: 11

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

African (AFR) AF: 0.396 AC: 7604 AN: 19206

American (AMR) AF: 0.543 AC: 4791 AN: 8828

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 895 AN: 1958

East Asian (EAS) AF: 0.655 AC: 2716 AN: 4144

South Asian (SAS) AF: 0.390 AC: 892 AN: 2290

European-Finnish (FIN) AF: 0.384 AC: 1993 AN: 5186

Middle Eastern (MID) AF: 0.478 AC: 89 AN: 186

European-Non Finnish (NFE) AF: 0.424 AC: 17692 AN: 41730

Other (OTH) AF: 0.448 AC: 501 AN: 1118

Alfa AF: 0.328 Hom.: 25982

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.32
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: rs1892593; hg19: chr21-35826360;