rs81204

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.1732+43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,598,214 control chromosomes in the GnomAD database, including 43,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3606 hom., cov: 33)

Exomes 𝑓: 0.23 ( 39402 hom. )

Consequence

KCNQ1
NM_000218.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.37

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 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=-0.91).

BP6

Variant 11-2777075-T-C is Benign according to our data. Variant chr11-2777075-T-C is described in ClinVar as Benign. ClinVar VariationId is 1291253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3 link	c.1732+43T>C		intron_variant	Intron 14 of 15	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12 link	c.1732+43T>C		intron_variant	Intron 14 of 15	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32248

AN:

151962

Hom.:

3596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.226

AC:

55693

AN:

246608

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.232

AC:

335677

AN:

1446134

Hom.:

39402

Cov.:

AF XY:

0.232

AC XY:

167115

AN XY:

720132

show subpopulations

African (AFR)

AF:

0.140

AC:

4654

AN:

33138

American (AMR)

AF:

0.197

AC:

8755

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

5922

AN:

26016

East Asian (EAS)

AF:

0.224

AC:

8872

AN:

39558

South Asian (SAS)

AF:

0.221

AC:

18927

AN:

85578

European-Finnish (FIN)

AF:

0.254

AC:

13520

AN:

53238

Middle Eastern (MID)

AF:

0.180

AC:

1033

AN:

5746

European-Non Finnish (NFE)

AF:

0.237

AC:

259814

AN:

1098512

Other (OTH)

AF:

0.237

AC:

14180

AN:

59888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14345

28690

43034

57379

71724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8800

17600

26400

35200

44000

<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:

0.212

AC:

32300

AN:

152080

Hom.:

3606

Cov.:

AF XY:

0.213

AC XY:

15814

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.144

AC:

5977

AN:

41480

American (AMR)

AF:

0.225

AC:

3435

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

783

AN:

3470

East Asian (EAS)

AF:

0.258

AC:

1332

AN:

5160

South Asian (SAS)

AF:

0.221

AC:

1067

AN:

4818

European-Finnish (FIN)

AF:

0.253

AC:

2675

AN:

10576

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16232

AN:

67984

Other (OTH)

AF:

0.242

AC:

508

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1304

2608

3911

5215

6519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.226

Hom.:

5479

Bravo

AF:

0.205

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.052

(source)

DANN

Benign

0.49

PhyloP100

-3.4

PromoterAI

0.0016

Neutral

(source)

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