11-2610111-T-C

Position:

• chr11-2610111-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000218.3(KCNQ1):​c.1393+21257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 397,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (1 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.438

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:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-2610111-T-C is Benign according to our data. Variant chr11-2610111-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1711272.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.1393+21257T>C		intron_variant		ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1393+21257T>C		intron_variant		1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 439 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00548

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00456

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00381 AC: 937 AN: 245724 Hom.: 1 Cov.: 0 AF XY: 0.00398 AC XY: 496 AN XY: 124548

Gnomad4 AFR exome AF: 0.000419

Gnomad4 AMR exome AF: 0.00229

Gnomad4 ASJ exome AF: 0.00456

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00351

Gnomad4 NFE exome AF: 0.00472

Gnomad4 OTH exome AF: 0.00349

GnomAD4 genome AF: 0.00288 AC: 439 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.00286 AC XY: 213 AN XY: 74470

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00548

Gnomad4 NFE AF: 0.00456

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00408 Hom.: 0

Bravo AF: 0.00263

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

KCNQ1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.4
DANN	Benign	0.90

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: rs190484983; hg19: chr11-2631341;