rs231362

Variant names:

• chr11-2670241-A-G
• rs231362
• NM_000218.3:c.1514+8160A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-2670241-A-G
• chr11-2670241-A-C
• chr11-2670241-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000218.3(KCNQ1):​c.1514+8160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 398,376 control chromosomes in the GnomAD database, including 74,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31027 hom., cov: 32)
  • Exomes 𝑓: 0.58 (43238 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.707
• Publications: 178 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-2670241-A-G is Benign according to our data. Variant chr11-2670241-A-G is described in ClinVar as Benign. ClinVar VariationId is 1256894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 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+8160A>G		intron	N/A	NP_000209.2
	KCNQ1OT1	NR_002728.4	MANE Select	n.29754T>C		non_coding_transcript_exon	Exon 1 of 1
	KCNQ1	NM_001406836.1		c.1418+8160A>G		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+8160A>G		intron	N/A	ENSP00000155840.2	P51787-1
	KCNQ1	ENST00000335475.6	TSL:1	c.1133+8160A>G		intron	N/A	ENSP00000334497.5	P51787-2
	KCNQ1OT1	ENST00000597346.1	TSL:6 MANE Select	n.29754T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94954 AN: 151936 Hom.: 30982 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.579 AC: 142692 AN: 246322 Hom.: 43238 Cov.: 0 AF XY: 0.577 AC XY: 72040 AN XY: 124814

African (AFR) AF: 0.773 AC: 5549 AN: 7182

American (AMR) AF: 0.670 AC: 4981 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 5788 AN: 9240

East Asian (EAS) AF: 0.901 AC: 20624 AN: 22894

South Asian (SAS) AF: 0.763 AC: 2307 AN: 3024

European-Finnish (FIN) AF: 0.508 AC: 10578 AN: 20824

Middle Eastern (MID) AF: 0.600 AC: 777 AN: 1294

European-Non Finnish (NFE) AF: 0.520 AC: 82185 AN: 158054

Other (OTH) AF: 0.605 AC: 9903 AN: 16376

GnomAD4 genome AF: 0.625 AC: 95063 AN: 152054 Hom.: 31027 Cov.: 32 AF XY: 0.630 AC XY: 46815 AN XY: 74316

African (AFR) AF: 0.782 AC: 32431 AN: 41472

American (AMR) AF: 0.649 AC: 9921 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3466

East Asian (EAS) AF: 0.895 AC: 4626 AN: 5168

South Asian (SAS) AF: 0.751 AC: 3615 AN: 4816

European-Finnish (FIN) AF: 0.514 AC: 5438 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34984 AN: 67960

Other (OTH) AF: 0.621 AC: 1309 AN: 2108

Alfa AF: 0.564 Hom.: 80282

Bravo AF: 0.644

Asia WGS AF: 0.793 AC: 2757 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	KCNQ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.072
DANN	Benign	0.53
PhyloP100		-0.71
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: rs231362; hg19: chr11-2691471;