dbSNP rs81204: KCNQ1:c.1732+43T>C (chr11-2777075-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1291253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2777075-T-C is described in Lovd as [Benign].

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	P51787-1Q96AI9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNQ1	ENST00000155840.12 link	c.1732+43T>C	intron_variant	Intron 14 of 15	1	NM_000218.3	ENSP00000155840.2	P51787-1
KCNQ1	ENST00000335475.6 link	c.1351+43T>C	intron_variant	Intron 14 of 15	1		ENSP00000334497.5	P51787-2
KCNQ1	ENST00000496887.7 link	c.1375+43T>C	intron_variant	Intron 14 of 15	5		ENSP00000434560.2	E9PPZ0
KCNQ1	ENST00000646564.2 link	c.1192+43T>C	intron_variant	Intron 9 of 10			ENSP00000495806.2	A0A2R8YEQ9

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

GnomAD3 exomes

AF:

0.226

AC:

55693

AN:

246608

Hom.:

6389

AF XY:

0.228

AC XY:

30474

AN XY:

133428

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 SAS exome

AF:

0.224

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

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.212

AC:

32300

AN:

152080

Hom.:

3606

Cov.:

AF XY:

0.213

AC XY:

15814

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.229

Hom.:

4377

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

DANN

Benign

0.49

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