rs11823023

chr11-2531539-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000218.3(KCNQ1):c.477+3521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,174 control chromosomes in the GnomAD database, including 2,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2342 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.103

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-2531539-G-A is Benign according to our data. Variant chr11-2531539-G-A is described in ClinVar as [Benign]. Clinvar id is 1164891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.477+3521G>A		intron_variant		ENST00000155840.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.477+3521G>A		intron_variant		1	NM_000218.3	P1
KCNQ1	ENST00000335475.6	c.96+3521G>A		intron_variant		1
KCNQ1	ENST00000496887.7	c.216+3521G>A		intron_variant		5
KCNQ1	ENST00000646564.2	c.477+3521G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25812 AN: 152056 Hom.: 2333 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.170 AC: 25825 AN: 152174 Hom.: 2342 Cov.: 33 AF XY: 0.168 AC XY: 12499 AN XY: 74388

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.188

Alfa AF: 0.180 Hom.: 401

Bravo AF: 0.165

Asia WGS AF: 0.0980 AC: 346 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.5
Dann	Benign	0.75

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: rs11823023; hg19: chr11-2552769;