rs45460605

Positions:

chr11-2848414-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000218.3(KCNQ1):c.*411C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 477,920 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 118 hom., cov: 33)

Exomes 𝑓: 0.023 ( 120 hom. )

Consequence

KCNQ1
NM_000218.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.667

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 11-2848414-C-T is Benign according to our data. Variant chr11-2848414-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 304247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3 linkuse as main transcript	c.*411C>T		3_prime_UTR_variant	16/16	ENST00000155840.12
KCNQ1-AS1	NR_130721.1 linkuse as main transcript	n.778-7972G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12 linkuse as main transcript	c.*411C>T	3_prime_UTR_variant	16/16	1	NM_000218.3	P1	P51787-1
KCNQ1	ENST00000335475.6 linkuse as main transcript	c.*411C>T	3_prime_UTR_variant	16/16	1			P51787-2
KCNQ1-AS1	ENST00000440887.2 linkuse as main transcript	n.777-7972G>A	intron_variant, non_coding_transcript_variant		5
KCNQ1	ENST00000496887.7 linkuse as main transcript	c.*411C>T	3_prime_UTR_variant	16/16	5

Frequencies

GnomAD3 genomes

AF:

0.0338

AC:

5146

AN:

152156

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0600

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0382

GnomAD3 exomes

AF:

0.0230

AC:

2996

AN:

130102

Hom.:

AF XY:

0.0218

AC XY:

1547

AN XY:

70818

show subpopulations

Gnomad AFR exome

AF:

0.0621

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0436

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00643

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0227

AC:

7406

AN:

325646

Hom.:

120

Cov.:

AF XY:

0.0212

AC XY:

3884

AN XY:

183556

show subpopulations

Gnomad4 AFR exome

AF:

0.0622

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0429

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00620

Gnomad4 FIN exome

AF:

0.00703

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0271

GnomAD4 genome

AF:

0.0338

AC:

5145

AN:

152274

Hom.:

118

Cov.:

AF XY:

0.0318

AC XY:

2371

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0599

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0323

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Long QT syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Atrial fibrillation, familial, 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Jervell and Lange-Nielsen syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Short QT syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.6

DANN

Benign

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over