rs163150

chr11-2776090-A-Gchr11-2776090-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000218.3(KCNQ1):c.1685+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,522,216 control chromosomes in the GnomAD database, including 349,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33412 hom., cov: 33)
  • Exomes 𝑓: 0.68 (315674 hom.)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-2776090-A-G is Benign according to our data. Variant chr11-2776090-A-G is described in ClinVar as [Benign]. Clinvar id is 1264836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2776090-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.1685+36A>G		intron_variant		ENST00000155840.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.1685+36A>G		intron_variant		1	NM_000218.3	P1
KCNQ1	ENST00000335475.6	c.1304+36A>G		intron_variant		1
KCNQ1	ENST00000496887.7	c.1328+36A>G		intron_variant		5
KCNQ1	ENST00000646564.2	c.1145+36A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100422 AN: 151994 Hom.: 33369 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.647

GnomAD3 exomes AF: 0.668 AC: 101051 AN: 151238 Hom.: 34175 AF XY: 0.676 AC XY: 53955 AN XY: 79814

Gnomad AFR exome AF: 0.605

Gnomad AMR exome AF: 0.551

Gnomad ASJ exome AF: 0.679

Gnomad EAS exome AF: 0.708

Gnomad SAS exome AF: 0.727

Gnomad FIN exome AF: 0.747

Gnomad NFE exome AF: 0.678

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.678 AC: 929514 AN: 1370104 Hom.: 315674 Cov.: 25 AF XY: 0.680 AC XY: 459523 AN XY: 675698

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.704

Gnomad4 SAS exome AF: 0.728

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.673

GnomAD4 genome AF: 0.661 AC: 100522 AN: 152112 Hom.: 33412 Cov.: 33 AF XY: 0.665 AC XY: 49496 AN XY: 74388

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.650

Alfa AF: 0.663 Hom.: 12585

Bravo AF: 0.642

Asia WGS AF: 0.731 AC: 2541 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Long QT syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory - Cardiogenetics, CHU de Nantes

Aug 01, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.5
Dann	Benign	0.52

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: rs163150; hg19: chr11-2797320; COSMIC: COSV50126670; COSMIC: COSV50126670;