NM_000218.3:c.*479G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0380

Publications

14 publications found

Variant links:

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 links:

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

KCNQ1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3 link	c.*479G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000155840.12	NP_000209.2	P51787-1Q96AI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12 link	c.*479G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_000218.3	ENSP00000155840.2		P51787-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15675

AN:

152098

Hom.:

944

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.125

AC:

16412

AN:

131708

AF XY:

0.117

show subpopulations

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 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.:

AF XY:

0.105

AC XY:

18242

AN XY:

173828

show subpopulations

African (AFR)

AF:

0.101

AC:

881

AN:

8692

American (AMR)

AF:

0.263

AC:

7200

AN:

27342

Ashkenazi Jewish (ASJ)

AF:

0.0946

AC:

1036

AN:

10954

East Asian (EAS)

AF:

0.0642

AC:

600

AN:

9352

South Asian (SAS)

AF:

0.0930

AC:

5546

AN:

59658

European-Finnish (FIN)

AF:

0.121

AC:

1534

AN:

12640

Middle Eastern (MID)

AF:

0.0938

AC:

109

AN:

1162

European-Non Finnish (NFE)

AF:

0.0934

AC:

15068

AN:

161294

Other (OTH)

AF:

0.0972

AC:

1392

AN:

14326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1949

3898

5848

7797

9746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.103

AC:

15694

AN:

152216

Hom.:

945

Cov.:

AF XY:

0.105

AC XY:

7826

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0974

AC:

4044

AN:

41528

American (AMR)

AF:

0.170

AC:

2606

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0995

AC:

345

AN:

3468

East Asian (EAS)

AF:

0.0596

AC:

309

AN:

5186

South Asian (SAS)

AF:

0.0860

AC:

415

AN:

4828

European-Finnish (FIN)

AF:

0.121

AC:

1285

AN:

10604

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0925

AC:

6290

AN:

67978

Other (OTH)

AF:

0.105

AC:

223

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

711

1423

2134

2846

3557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not provided

Benign:2

May 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27531917, 22199116) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Long QT syndrome 1

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jervell and Lange-Nielsen syndrome 1

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Short QT syndrome type 2

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital long QT syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Long QT syndrome

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.4

(source)

DANN

Benign

0.42

PhyloP100

0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over