rs41314071

Variant names:

• chr21-34449113-T-C
• rs41314071
• NM_000219.6:c.*132A>G

Variant summary

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

The NM_000219.6(KCNE1):​c.*132A>G variant causes a 3 prime UTR 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 0.15 (4710 hom., cov: 16)
  • Exomes 𝑓: 0.085 (9312 hom.)
• Consequence: KCNE1 NM_000219.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.148
• Publications: 7 publications found

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]

KCNE1 Gene-Disease associations (from GenCC):

• long QT syndrome 5

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Jervell and Lange-Nielsen syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.93).
• BP6: Variant 21-34449113-T-C is Benign according to our data. Variant chr21-34449113-T-C is described in ClinVar as Benign. ClinVar VariationId is 339768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000219.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE1	NM_000219.6	MANE Select	c.*132A>G		3_prime_UTR	Exon 4 of 4	NP_000210.2	P15382
	KCNE1	NM_001127668.4		c.*132A>G		3_prime_UTR	Exon 3 of 3	NP_001121140.1	P15382
	KCNE1	NM_001127669.4		c.*132A>G		3_prime_UTR	Exon 3 of 3	NP_001121141.1	C7S316

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE1	ENST00000399286.3	TSL:1 MANE Select	c.*132A>G		3_prime_UTR	Exon 4 of 4	ENSP00000382226.2	P15382
	KCNE1	ENST00000399289.7	TSL:1	c.*132A>G		3_prime_UTR	Exon 3 of 3	ENSP00000382228.3	P15382
	KCNE1	ENST00000432085.5	TSL:1	c.*132A>G		3_prime_UTR	Exon 3 of 3	ENSP00000412498.1	P15382

Frequencies

GnomAD3 genomes AF: 0.146 AC: 16177 AN: 110746 Hom.: 4699 Cov.: 16

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0745

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0855 AC: 31270 AN: 365790 Hom.: 9312 Cov.: 3 AF XY: 0.0845 AC XY: 16306 AN XY: 193074

African (AFR) AF: 0.270 AC: 3395 AN: 12586

American (AMR) AF: 0.0458 AC: 938 AN: 20500

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 987 AN: 9988

East Asian (EAS) AF: 0.0141 AC: 337 AN: 23904

South Asian (SAS) AF: 0.0590 AC: 2045 AN: 34644

European-Finnish (FIN) AF: 0.0674 AC: 2405 AN: 35704

Middle Eastern (MID) AF: 0.114 AC: 206 AN: 1810

European-Non Finnish (NFE) AF: 0.0919 AC: 18968 AN: 206394

Other (OTH) AF: 0.0982 AC: 1989 AN: 20260

GnomAD4 genome AF: 0.146 AC: 16213 AN: 110856 Hom.: 4710 Cov.: 16 AF XY: 0.141 AC XY: 7605 AN XY: 53850

African (AFR) AF: 0.275 AC: 9389 AN: 34096

American (AMR) AF: 0.0684 AC: 763 AN: 11162

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 253 AN: 2422

East Asian (EAS) AF: 0.0342 AC: 109 AN: 3190

South Asian (SAS) AF: 0.0712 AC: 231 AN: 3244

European-Finnish (FIN) AF: 0.0630 AC: 489 AN: 7766

Middle Eastern (MID) AF: 0.133 AC: 28 AN: 210

European-Non Finnish (NFE) AF: 0.101 AC: 4698 AN: 46724

Other (OTH) AF: 0.143 AC: 211 AN: 1478

Alfa AF: 0.0928 Hom.: 540

Asia WGS AF: 0.0550 AC: 193 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.93
CADD	Benign	4.1
DANN	Benign	0.32
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41314071;

hg19: chr21-35821411;