rs800337

Variant names:

• chr11-2452081-T-C
• rs800337
• NM_000218.3:c.386+6597T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000218.3(KCNQ1):​c.386+6597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,142 control chromosomes in the GnomAD database, including 44,897 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 0.76 (44897 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 2 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]

KCNQ1 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• long QT syndrome 1

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Jervell and Lange-Nielsen syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• atrial fibrillation, familial, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short QT syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• short QT syndrome type 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	NM_000218.3	MANE Select	c.386+6597T>C		intron	N/A	NP_000209.2
	KCNQ1	NM_001406836.1		c.386+6597T>C		intron	N/A	NP_001393765.1
	KCNQ1	NM_001406837.1		c.24+6597T>C		intron	N/A	NP_001393766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.386+6597T>C		intron	N/A	ENSP00000155840.2
	KCNQ1	ENST00000345015.4	TSL:1	n.163+6597T>C		intron	N/A
	KCNQ1	ENST00000713725.1		c.386+6597T>C		intron	N/A	ENSP00000519029.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115965 AN: 152024 Hom.: 44874 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.763 AC: 116037 AN: 152142 Hom.: 44897 Cov.: 33 AF XY: 0.759 AC XY: 56455 AN XY: 74378

African (AFR) AF: 0.653 AC: 27102 AN: 41504

American (AMR) AF: 0.747 AC: 11413 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2745 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2973 AN: 5136

South Asian (SAS) AF: 0.579 AC: 2797 AN: 4830

European-Finnish (FIN) AF: 0.826 AC: 8755 AN: 10602

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.846 AC: 57541 AN: 67996

Other (OTH) AF: 0.772 AC: 1632 AN: 2114

Alfa AF: 0.783 Hom.: 16506

Bravo AF: 0.753

Asia WGS AF: 0.585 AC: 2034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.077
DANN	Benign	0.40
PhyloP100		-3.6
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: rs800337; hg19: chr11-2473311;