rs231352

Variant names:

• chr11-2689592-T-C
• rs231352
• NM_000218.3:c.1514+27511T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2689592-T-C
• chr11-2689592-T-A
• chr11-2689592-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000218.3(KCNQ1):​c.1514+27511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 398,460 control chromosomes in the GnomAD database, including 73,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.62 (31138 hom., cov: 33)
  • Exomes 𝑓: 0.57 (42723 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.42
• Publications: 16 publications found

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]

KCNQ1OT1 Gene-Disease associations (from GenCC):

• Beckwith-Wiedemann syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-2689592-T-C is Benign according to our data. Variant chr11-2689592-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060442.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	NM_000218.3	MANE Select	c.1514+27511T>C		intron	N/A	NP_000209.2
	KCNQ1OT1	NR_002728.4	MANE Select	n.10403A>G		non_coding_transcript_exon	Exon 1 of 1
	KCNQ1	NM_001406836.1		c.1418+27511T>C		intron	N/A	NP_001393765.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.1514+27511T>C		intron	N/A	ENSP00000155840.2	P51787-1
	KCNQ1	ENST00000335475.6	TSL:1	c.1133+27511T>C		intron	N/A	ENSP00000334497.5	P51787-2
	KCNQ1OT1	ENST00000597346.1	TSL:6 MANE Select	n.10403A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94917 AN: 151998 Hom.: 31086 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.574 AC: 141508 AN: 246344 Hom.: 42723 Cov.: 0 AF XY: 0.573 AC XY: 71561 AN XY: 124824

African (AFR) AF: 0.776 AC: 5574 AN: 7180

American (AMR) AF: 0.661 AC: 4914 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 5628 AN: 9240

East Asian (EAS) AF: 0.899 AC: 20574 AN: 22894

South Asian (SAS) AF: 0.848 AC: 2574 AN: 3034

European-Finnish (FIN) AF: 0.576 AC: 11997 AN: 20832

Middle Eastern (MID) AF: 0.594 AC: 768 AN: 1294

European-Non Finnish (NFE) AF: 0.504 AC: 79718 AN: 158064

Other (OTH) AF: 0.596 AC: 9761 AN: 16372

GnomAD4 genome AF: 0.625 AC: 95030 AN: 152116 Hom.: 31138 Cov.: 33 AF XY: 0.634 AC XY: 47119 AN XY: 74346

African (AFR) AF: 0.780 AC: 32393 AN: 41510

American (AMR) AF: 0.633 AC: 9670 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3470

East Asian (EAS) AF: 0.900 AC: 4666 AN: 5186

South Asian (SAS) AF: 0.840 AC: 4051 AN: 4822

European-Finnish (FIN) AF: 0.586 AC: 6195 AN: 10576

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34165 AN: 67948

Other (OTH) AF: 0.605 AC: 1277 AN: 2110

Alfa AF: 0.568 Hom.: 4328

Bravo AF: 0.634

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KCNQ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.68
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs231352; hg19: chr11-2710822;