11-2685097-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000218.3(KCNQ1):​c.1514+23016G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 398,524 control chromosomes in the GnomAD database, including 77,824 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 0.64 ( 32676 hom., cov: 33)
Exomes 𝑓: 0.58 ( 45148 hom. )

Consequence

KCNQ1
NM_000218.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.02
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNQ1NM_000218.3 linkc.1514+23016G>C intron_variant ENST00000155840.12 NP_000209.2 P51787-1Q96AI9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNQ1ENST00000155840.12 linkc.1514+23016G>C intron_variant 1 NM_000218.3 ENSP00000155840.2 P51787-1

Frequencies

GnomAD3 genomes
AF:
0.637
AC:
96900
AN:
152074
Hom.:
32615
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.802
Gnomad AMI
AF:
0.361
Gnomad AMR
AF:
0.667
Gnomad ASJ
AF:
0.597
Gnomad EAS
AF:
0.988
Gnomad SAS
AF:
0.847
Gnomad FIN
AF:
0.624
Gnomad MID
AF:
0.528
Gnomad NFE
AF:
0.497
Gnomad OTH
AF:
0.612
GnomAD4 exome
AF:
0.584
AC:
143979
AN:
246332
Hom.:
45148
Cov.:
0
AF XY:
0.582
AC XY:
72697
AN XY:
124826
show subpopulations
Gnomad4 AFR exome
AF:
0.790
Gnomad4 AMR exome
AF:
0.710
Gnomad4 ASJ exome
AF:
0.591
Gnomad4 EAS exome
AF:
0.995
Gnomad4 SAS exome
AF:
0.853
Gnomad4 FIN exome
AF:
0.615
Gnomad4 NFE exome
AF:
0.498
Gnomad4 OTH exome
AF:
0.607
GnomAD4 genome
AF:
0.638
AC:
97026
AN:
152192
Hom.:
32676
Cov.:
33
AF XY:
0.649
AC XY:
48269
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.802
Gnomad4 AMR
AF:
0.667
Gnomad4 ASJ
AF:
0.597
Gnomad4 EAS
AF:
0.988
Gnomad4 SAS
AF:
0.848
Gnomad4 FIN
AF:
0.624
Gnomad4 NFE
AF:
0.498
Gnomad4 OTH
AF:
0.617
Alfa
AF:
0.569
Hom.:
2813
Bravo
AF:
0.646
Asia WGS
AF:
0.889
AC:
3091
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.18
DANN
Benign
0.42

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.

Other links and lift over

dbSNP: rs231355; hg19: chr11-2706327; API