rs2070358

Positions:

• chr21-34449972-T-C
• chr21-34449972-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000219.6(KCNE1):​c.-50-288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.014 (31 hom., cov: 12)
• Consequence: KCNE1 NM_000219.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.46

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-34449972-T-C is Benign according to our data. Variant chr21-34449972-T-C is described in ClinVar as [Benign]. Clinvar id is 675606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.014 (1109/79036) while in subpopulation EAS AF= 0.0263 (47/1784). AF 95% confidence interval is 0.0204. There are 31 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.-50-288A>G		intron_variant		ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3	c.-50-288A>G		intron_variant		1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 1105 AN: 78956 Hom.: 31 Cov.: 12

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00356

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0140

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0131

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

GnomAD4 genome AF: 0.0140 AC: 1109 AN: 79036 Hom.: 31 Cov.: 12 AF XY: 0.0138 AC XY: 531 AN XY: 38366

Gnomad4 AFR AF: 0.00860

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0140

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0130

Alfa AF: 0.597 Hom.: 37273

Asia WGS AF: 0.590 AC: 2056 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Long QT syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.43

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: rs2070358; hg19: chr21-35822270;