rs2519184

Positions:

• chr11-2848482-G-A
• chr11-2848482-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000218.3(KCNQ1):​c.*479G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 457,636 control chromosomes in the GnomAD database, including 3,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (945 hom., cov: 34)
  • Exomes 𝑓: 0.11 (2450 hom.)
• Consequence: KCNQ1 NM_000218.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0380

Genes affected

KCNQ1 (HGNC:6294): (potassium voltage-gated channel subfamily Q member 1) This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

KCNQ1-AS1 (HGNC:42790): (KCNQ1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-2848482-G-A is Benign according to our data. Variant chr11-2848482-G-A is described in ClinVar as [Benign]. Clinvar id is 304249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.*479G>A		3_prime_UTR_variant	16/16	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.*479G>A		3_prime_UTR_variant	16/16	1	NM_000218.3	ENSP00000155840.2
KCNQ1	ENST00000335475.6	c.*479G>A		3_prime_UTR_variant	16/16	1		ENSP00000334497.5
KCNQ1	ENST00000496887.7	c.*479G>A		3_prime_UTR_variant	16/16	5		ENSP00000434560.2
KCNQ1-AS1	ENST00000440887.2	n.777-8040C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15675 AN: 152098 Hom.: 944 Cov.: 34

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.125 AC: 16412 AN: 131708 Hom.: 1479 AF XY: 0.117 AC XY: 8410 AN XY: 71618

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.0927

Gnomad EAS exome AF: 0.0659

Gnomad SAS exome AF: 0.0944

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.0929

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.109 AC: 33366 AN: 305420 Hom.: 2450 Cov.: 0 AF XY: 0.105 AC XY: 18242 AN XY: 173828

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.0946

Gnomad4 EAS exome AF: 0.0642

Gnomad4 SAS exome AF: 0.0930

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0934

Gnomad4 OTH exome AF: 0.0972

GnomAD4 genome AF: 0.103 AC: 15694 AN: 152216 Hom.: 945 Cov.: 34 AF XY: 0.105 AC XY: 7826 AN XY: 74424

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.0596

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0698 Hom.: 118

Bravo AF: 0.108

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	This variant is associated with the following publications: (PMID: 27531917, 22199116) -

Long QT syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Atrial fibrillation, familial, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Jervell and Lange-Nielsen syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Short QT syndrome type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.42

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: rs2519184; hg19: chr11-2869712;