rs2075870

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.1515-55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 1,373,006 control chromosomes in the GnomAD database, including 2,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene KCNQ1 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.055 ( 401 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1861 hom. )

Consequence

KCNQ1
NM_000218.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.461

Publications

11 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: G2P, Labcorp Genetics (formerly Invitae)
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:

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ACMG classification

Specifications for KCNQ1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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 11-2768789-G-A is Benign according to our data. Variant chr11-2768789-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000218.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNQ1	NM_000218.3	MANE Select	c.1515-55G>A	intron	N/A	NP_000209.2
KCNQ1	NM_001406836.1		c.1419-55G>A	intron	N/A	NP_001393765.1
KCNQ1	NM_001406837.1		c.1245-55G>A	intron	N/A	NP_001393766.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.1515-55G>A	intron	N/A	ENSP00000155840.2	P51787-1
KCNQ1	ENST00000335475.6	TSL:1	c.1134-55G>A	intron	N/A	ENSP00000334497.5	P51787-2
KCNQ1	ENST00000910997.1		c.1512-55G>A	intron	N/A	ENSP00000581056.1

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8279

AN:

152096

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0992

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0917

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.0888

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0603

GnomAD4 exome

AF:

0.0365

AC:

44597

AN:

1220792

Hom.:

1861

AF XY:

0.0379

AC XY:

23484

AN XY:

619172

show subpopulations

African (AFR)

AF:

0.108

AC:

3114

AN:

28750

American (AMR)

AF:

0.0220

AC:

975

AN:

44344

Ashkenazi Jewish (ASJ)

AF:

0.0958

AC:

2361

AN:

24646

East Asian (EAS)

AF:

0.209

AC:

8066

AN:

38588

South Asian (SAS)

AF:

0.0817

AC:

6653

AN:

81430

European-Finnish (FIN)

AF:

0.00641

AC:

341

AN:

53192

Middle Eastern (MID)

AF:

0.0636

AC:

338

AN:

5312

European-Non Finnish (NFE)

AF:

0.0226

AC:

20201

AN:

892118

Other (OTH)

AF:

0.0486

AC:

2548

AN:

52412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2314

4628

6941

9255

11569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.0545

AC:

8298

AN:

152214

Hom.:

401

Cov.:

AF XY:

0.0546

AC XY:

4062

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0995

AC:

4133

AN:

41530

American (AMR)

AF:

0.0322

AC:

492

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0917

AC:

318

AN:

3468

East Asian (EAS)

AF:

0.208

AC:

1076

AN:

5162

South Asian (SAS)

AF:

0.0882

AC:

425

AN:

4818

European-Finnish (FIN)

AF:

0.00386

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0246

AC:

1675

AN:

68000

Other (OTH)

AF:

0.0606

AC:

128

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

384

767

1151

1534

1918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0353

Hom.:

Bravo

AF:

0.0594

Asia WGS

AF:

0.115

AC:

401

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.79

(source)

DANN

Benign

0.76

PhyloP100

0.46

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over