21-34512227-G-A

Position:

• chr21-34512227-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 339790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34512227-G-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
		n.34512227G>A		intergenic_region
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/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000288711	ENST00000684114.1	n.488-9C>T		intron_variant				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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.248

Alfa AF: 0.247 Hom.: 2847

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Congenital long QT syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Long QT syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Jervell and Lange-Nielsen syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11702354; hg19: chr21-35884525;