rs2834502

Variant names:

• chr21-34511191-C-T
• rs2834502
• ENST00000684114.1:n.*294G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000684114.1(ENSG00000288711):​n.*294G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 985,406 control chromosomes in the GnomAD database, including 27,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4172 hom., cov: 32)
  • Exomes 𝑓: 0.23 (22992 hom.)
• Consequence: ENSG00000288711 ENST00000684114.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.268
• Publications: 8 publications found

Genes affected

ENSG00000288711 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-34511191-C-T is Benign according to our data. Variant chr21-34511191-C-T is described in ClinVar as Benign. ClinVar VariationId is 339779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000684114.1. 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
	KCNE1	NM_000219.6	MANE Select	c.-252G>A		5_prime_UTR	Exon 2 of 4	NP_000210.2
	KCNE1	NM_001270402.3		c.-252G>A		5_prime_UTR	Exon 1 of 3	NP_001257331.1
	KCNE1	NM_001270403.2		c.-224G>A		5_prime_UTR	Exon 1 of 3	NP_001257332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000288711	ENST00000684114.1		n.*294G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000507841.1
	KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.-252G>A		5_prime_UTR	Exon 2 of 4	ENSP00000382226.2
	ENSG00000288711	ENST00000684114.1		n.*294G>A		3_prime_UTR	Exon 5 of 5	ENSP00000507841.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31417 AN: 152088 Hom.: 4170 Cov.: 32

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.232 AC: 193398 AN: 833200 Hom.: 22992 Cov.: 30 AF XY: 0.231 AC XY: 88942 AN XY: 384860

African (AFR) AF: 0.0377 AC: 596 AN: 15796

American (AMR) AF: 0.367 AC: 361 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 1269 AN: 5152

East Asian (EAS) AF: 0.504 AC: 1835 AN: 3642

South Asian (SAS) AF: 0.176 AC: 2896 AN: 16464

European-Finnish (FIN) AF: 0.241 AC: 67 AN: 278

Middle Eastern (MID) AF: 0.225 AC: 366 AN: 1624

European-Non Finnish (NFE) AF: 0.235 AC: 179331 AN: 761950

Other (OTH) AF: 0.244 AC: 6677 AN: 27310

GnomAD4 genome AF: 0.206 AC: 31420 AN: 152206 Hom.: 4172 Cov.: 32 AF XY: 0.211 AC XY: 15691 AN XY: 74410

African (AFR) AF: 0.0575 AC: 2389 AN: 41566

American (AMR) AF: 0.329 AC: 5034 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3470

East Asian (EAS) AF: 0.520 AC: 2684 AN: 5166

South Asian (SAS) AF: 0.199 AC: 957 AN: 4816

European-Finnish (FIN) AF: 0.238 AC: 2521 AN: 10592

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16265 AN: 67980

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.235 Hom.: 13239

Bravo AF: 0.214

Asia WGS AF: 0.329 AC: 1140 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Jervell and Lange-Nielsen syndrome 2 (1)
-	-	1	Long QT syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		0.27
PromoterAI		-0.0067	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2834502; hg19: chr21-35883489;