rs11024304

Variant names:

• chr11-2841715-C-T
• rs11024304
• NM_000218.3:c.1795-6052C>T

Variant summary

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

The NM_000218.3(KCNQ1):​c.1795-6052C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,234 control chromosomes in the GnomAD database, including 638 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 0.074 (638 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• 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-AS1 (HGNC:42790): (KCNQ1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1795-6052C>T		intron_variant	Intron 15 of 15	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1795-6052C>T		intron_variant	Intron 15 of 15	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11209 AN: 152114 Hom.: 639 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0736 AC: 11207 AN: 152234 Hom.: 638 Cov.: 33 AF XY: 0.0753 AC XY: 5602 AN XY: 74432

African (AFR) AF: 0.139 AC: 5754 AN: 41524

American (AMR) AF: 0.0478 AC: 731 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1075 AN: 5176

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4828

European-Finnish (FIN) AF: 0.0541 AC: 574 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0366 AC: 2492 AN: 68008

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0520 Hom.: 985

Bravo AF: 0.0768

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		-0.70
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: rs11024304; hg19: chr11-2862945;