11-2789501-C-T

Variant names:

• chr11-2789501-C-T
• rs2237886
• NM_000218.3:c.1794+11464C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000218.3(KCNQ1):​c.1794+11464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,270 control chromosomes in the GnomAD database, including 763 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 0.094 (763 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1794+11464C>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.1794+11464C>T		intron_variant	Intron 15 of 15	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14383 AN: 152152 Hom.: 762 Cov.: 33

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0945 AC: 14389 AN: 152270 Hom.: 763 Cov.: 33 AF XY: 0.0967 AC XY: 7201 AN XY: 74448

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.0993

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0969 Hom.: 1737

Bravo AF: 0.0933

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.010
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs2237886; hg19: chr11-2810731;