rs11702354

Variant names:

• chr21-34512227-G-A
• rs11702354
• ENST00000684114.1:n.488-9C>T

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.488-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,182 control chromosomes in the GnomAD database, including 4,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4813 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1 hom.)
• Consequence: ENSG00000288711 ENST00000684114.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0500
• Publications: 11 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=-0.82).
• BP6: Variant 21-34512227-G-A is Benign according to our data. Variant chr21-34512227-G-A is described in ClinVar as Benign. ClinVar VariationId is 339790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.-577C>T		upstream_gene_variant		ENST00000399286.3	NP_000210.2
KCNE1	XM_047440764.1	c.-540C>T		upstream_gene_variant			XP_047296720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288711	ENST00000684114.1	n.488-9C>T		intron_variant	Intron 3 of 4			ENSP00000507841.1
KCNE1	ENST00000399286.3	c.-577C>T		upstream_gene_variant		1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35737 AN: 152032 Hom.: 4811 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.156 AC: 5 AN: 32 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 5 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.136 AC: 3 AN: 22

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.235 AC: 35742 AN: 152150 Hom.: 4813 Cov.: 32 AF XY: 0.238 AC XY: 17695 AN XY: 74386

African (AFR) AF: 0.129 AC: 5353 AN: 41512

American (AMR) AF: 0.352 AC: 5379 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2672 AN: 5166

South Asian (SAS) AF: 0.208 AC: 1001 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2409 AN: 10600

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17195 AN: 67980

Other (OTH) AF: 0.248 AC: 523 AN: 2108

Alfa AF: 0.246 Hom.: 3099

Bravo AF: 0.247

Asia WGS AF: 0.334 AC: 1158 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital long QT syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jervell and Lange-Nielsen syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		0.050
PromoterAI		-0.016	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11702354; hg19: chr21-35884525;