rs2236609

Positions:

• chr21-34449813-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000219.6(KCNE1):​c.-50-129T>C 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 0.0050 (7 hom., cov: 11)
  • Exomes 𝑓: 0.000047 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNE1 NM_000219.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.35

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 21-34449813-A-G is Benign according to our data. Variant chr21-34449813-A-G is described in ClinVar as [Benign]. Clinvar id is 671896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE1	NM_000219.6	c.-50-129T>C		intron_variant		ENST00000399286.3	NP_000210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE1	ENST00000399286.3	c.-50-129T>C		intron_variant		1	NM_000219.6	ENSP00000382226.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 385 AN: 78040 Hom.: 6 Cov.: 11 FAILED QC

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0148

Gnomad AMR AF: 0.00685

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00515

Gnomad SAS AF: 0.00732

Gnomad FIN AF: 0.00420

Gnomad MID AF: 0.00581

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.00282

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000467 AC: 15 AN: 321114 Hom.: 4 AF XY: 0.0000421 AC XY: 7 AN XY: 166290

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000260

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000755

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00498 AC: 389 AN: 78078 Hom.: 7 Cov.: 11 AF XY: 0.00544 AC XY: 206 AN XY: 37862

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.00683

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00517

Gnomad4 SAS AF: 0.00735

Gnomad4 FIN AF: 0.00420

Gnomad4 NFE AF: 0.00221

Gnomad4 OTH AF: 0.00279

Alfa AF: 0.413 Hom.: 3568

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0010
DANN	Benign	0.32

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: rs2236609; hg19: chr21-35822111;