rs163150

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1685+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,522,216 control chromosomes in the GnomAD database, including 349,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33412 hom., cov: 33)

Exomes 𝑓: 0.68 ( 315674 hom. )

Consequence

KCNQ1
NM_000218.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.25

Publications

18 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 Gene-Disease associations (from GenCC):

long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 1
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Jervell and Lange-Nielsen syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
atrial fibrillation, familial, 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
short QT syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
short QT syndrome type 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNQ1 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=-0.96).

BP6

Variant 11-2776090-A-G is Benign according to our data. Variant chr11-2776090-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3 link	c.1685+36A>G		intron_variant	Intron 13 of 15	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.1685+36A>G		intron_variant	Intron 13 of 15	1	NM_000218.3	ENSP00000155840.2		P51787-1

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100422

AN:

151994

Hom.:

33369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.620

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.590

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.647

GnomAD2 exomes

AF:

0.668

AC:

101051

AN:

151238

AF XY:

0.676

show subpopulations

Gnomad AFR exome

AF:

0.605

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.679

Gnomad EAS exome

AF:

0.708

Gnomad FIN exome

AF:

0.747

Gnomad NFE exome

AF:

0.678

Gnomad OTH exome

AF:

0.661

GnomAD4 exome

AF:

0.678

AC:

929514

AN:

1370104

Hom.:

315674

Cov.:

AF XY:

0.680

AC XY:

459523

AN XY:

675698

show subpopulations

African (AFR)

AF:

0.620

AC:

19319

AN:

31182

American (AMR)

AF:

0.555

AC:

19723

AN:

35566

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

16879

AN:

24842

East Asian (EAS)

AF:

0.704

AC:

25033

AN:

35556

South Asian (SAS)

AF:

0.728

AC:

57284

AN:

78668

European-Finnish (FIN)

AF:

0.736

AC:

33372

AN:

45316

Middle Eastern (MID)

AF:

0.646

AC:

2834

AN:

4388

European-Non Finnish (NFE)

AF:

0.678

AC:

716726

AN:

1057602

Other (OTH)

AF:

0.673

AC:

38344

AN:

56984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

15629

31259

46888

62518

78147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18692

37384

56076

74768

93460

<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:

0.661

AC:

100522

AN:

152112

Hom.:

33412

Cov.:

AF XY:

0.665

AC XY:

49496

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.621

AC:

25762

AN:

41472

American (AMR)

AF:

0.590

AC:

9022

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

2392

AN:

3472

East Asian (EAS)

AF:

0.709

AC:

3652

AN:

5154

South Asian (SAS)

AF:

0.735

AC:

3543

AN:

4818

European-Finnish (FIN)

AF:

0.735

AC:

7800

AN:

10610

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.681

AC:

46272

AN:

67986

Other (OTH)

AF:

0.650

AC:

1370

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1783

3565

5348

7130

8913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.662

Hom.:

15044

Bravo

AF:

0.642

Asia WGS

AF:

0.731

AC:

2541

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Long QT syndrome 1

Benign:1

Aug 01, 2023

Molecular Genetics Laboratory - Cardiogenetics, CHU de Nantes

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

-0.96

CADD

Benign

2.5

(source)

DANN

Benign

0.52

PhyloP100

-1.2

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

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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