11-2661922-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000218.3(KCNQ1):c.1394-39T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,768 control chromosomes in the GnomAD database, including 13,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3776 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9345 hom. )

Consequence

KCNQ1
NM_000218.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273

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 links:

KCNQ1OT1 (HGNC:6295): (KCNQ1 opposite strand/antisense transcript 1) Human chromosomal region 11p15.5 contains two clusters of epigenetically-regulated genes that are expressed from only one chromosome in a parent-of-origin manner. Each cluster, or imprinted domain, is regulated by a functionally independent imprinting control region (ICR). The human CDKN1C/KCNQ1OT1 domain is regulated by an ICR located in an intron of KCNQ1, and contains at least eight genes that are expressed exclusively or preferentially from the maternally-inherited allele. The DNA of the ICR is specifically methylated on the maternally-inherited chromosome, and unmethylated on the paternally-inherited chromosome. The ICR contains the promoter of the KCNQ1OT1 gene that is exclusively expressed from the paternal allele. The KCNQ1OT1 transcript is the antisense to the KCNQ1 gene and is a unspliced long non-coding RNA. It interacts with chromatin and regulates transcription of multiple target genes through epigenetic modifications. The transcript is abnormally expressed from both chromosomes in most patients with Beckwith-Wiedemann syndrome, and the transcript also plays an important role in colorectal carcinogenesis. [provided by RefSeq, Apr 2012]

KCNQ1OT1 Gene-Disease associations (from GenCC):

Beckwith-Wiedemann syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

KCNQ1OT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 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.1394-39T>G	intron	N/A	NP_000209.2
KCNQ1OT1	NR_002728.4	MANE Select	n.38073A>C	non_coding_transcript_exon	Exon 1 of 1
KCNQ1	NM_001406836.1		c.1298-39T>G	intron	N/A	NP_001393765.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.1394-39T>G	intron	N/A	ENSP00000155840.2
KCNQ1	ENST00000335475.6	TSL:1	c.1013-39T>G	intron	N/A	ENSP00000334497.5
KCNQ1OT1	ENST00000597346.1	TSL:6 MANE Select	n.38073A>C	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27052

AN:

151926

Hom.:

3752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0537

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0916

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.116

AC:

28924

AN:

249838

AF XY:

0.113

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.0761

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0546

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.0911

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0997

AC:

145679

AN:

1460724

Hom.:

9345

Cov.:

AF XY:

0.101

AC XY:

73088

AN XY:

726688

show subpopulations

African (AFR)

AF:

0.403

AC:

13495

AN:

33448

American (AMR)

AF:

0.0793

AC:

3545

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2710

AN:

26130

East Asian (EAS)

AF:

0.0514

AC:

2041

AN:

39684

South Asian (SAS)

AF:

0.147

AC:

12657

AN:

86232

European-Finnish (FIN)

AF:

0.111

AC:

5877

AN:

52842

Middle Eastern (MID)

AF:

0.0888

AC:

512

AN:

5764

European-Non Finnish (NFE)

AF:

0.0884

AC:

98227

AN:

1111554

Other (OTH)

AF:

0.110

AC:

6615

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

6859

13718

20577

27436

34295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3856

7712

11568

15424

19280

<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:

0.178

AC:

27122

AN:

152044

Hom.:

3776

Cov.:

AF XY:

0.175

AC XY:

13033

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.392

AC:

16265

AN:

41442

American (AMR)

AF:

0.114

AC:

1751

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

374

AN:

3472

East Asian (EAS)

AF:

0.0538

AC:

278

AN:

5166

South Asian (SAS)

AF:

0.147

AC:

708

AN:

4810

European-Finnish (FIN)

AF:

0.100

AC:

1060

AN:

10580

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0916

AC:

6223

AN:

67964

Other (OTH)

AF:

0.164

AC:

346

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1003

2006

3009

4012

5015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.0964

Hom.:

303

Bravo

AF:

0.187

Asia WGS

AF:

0.137

AC:

477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.11

(source)

DANN

Benign

0.83

PhyloP100

0.27

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