chr11-2848935-A-G

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.*932A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 453,978 control chromosomes in the GnomAD database, including 38,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12221 hom., cov: 34)

Exomes 𝑓: 0.39 ( 25979 hom. )

Consequence

KCNQ1
NM_000218.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.06

Publications

27 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=-0.82).

BP6

Variant 11-2848935-A-G is Benign according to our data. Variant chr11-2848935-A-G is described in ClinVar as [Benign]. Clinvar id is 304268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3 link	c.*932A>G		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.*932A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_000218.3	ENSP00000155840.2		P51787-1

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58641

AN:

152064

Hom.:

12212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.403

GnomAD2 exomes

AF:

0.445

AC:

58052

AN:

130500

AF XY:

0.440

show subpopulations

Gnomad AFR exome

AF:

0.414

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.872

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.394

AC:

118970

AN:

301796

Hom.:

25979

Cov.:

AF XY:

0.400

AC XY:

68735

AN XY:

171996

show subpopulations

African (AFR)

AF:

0.409

AC:

3496

AN:

8554

American (AMR)

AF:

0.552

AC:

15051

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

4109

AN:

10786

East Asian (EAS)

AF:

0.870

AC:

8009

AN:

9210

South Asian (SAS)

AF:

0.478

AC:

28516

AN:

59650

European-Finnish (FIN)

AF:

0.367

AC:

4541

AN:

12368

Middle Eastern (MID)

AF:

0.390

AC:

449

AN:

1150

European-Non Finnish (NFE)

AF:

0.311

AC:

49407

AN:

158762

Other (OTH)

AF:

0.384

AC:

5392

AN:

14042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6758

13516

20273

27031

33789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.386

AC:

58693

AN:

152182

Hom.:

12221

Cov.:

AF XY:

0.394

AC XY:

29304

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.405

AC:

16826

AN:

41498

American (AMR)

AF:

0.473

AC:

7239

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1335

AN:

3466

East Asian (EAS)

AF:

0.859

AC:

4440

AN:

5170

South Asian (SAS)

AF:

0.492

AC:

2376

AN:

4830

European-Finnish (FIN)

AF:

0.372

AC:

3940

AN:

10592

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.312

AC:

21248

AN:

68016

Other (OTH)

AF:

0.404

AC:

855

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1837

3674

5511

7348

9185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.346

Hom.:

16930

Bravo

AF:

0.396

Asia WGS

AF:

0.632

AC:

2193

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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) -

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 30, 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

-0.82

CADD

Benign

0.51

(source)

DANN

Benign

0.70

PhyloP100

-2.1

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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chr11-2848935-A-G

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