11-2532919-A-G

Position:

• chr11-2532919-A-G

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+4901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,096 control chromosomes in the GnomAD database, including 49,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49407 hom., cov: 33)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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=-0.83).
• BP6: Variant 11-2532919-A-G is Benign according to our data. Variant chr11-2532919-A-G is described in ClinVar as [Benign]. Clinvar id is 1164892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ1	NM_000218.3	c.477+4901A>G		intron_variant		ENST00000155840.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ1	ENST00000155840.12	c.477+4901A>G		intron_variant		1	NM_000218.3	P1
KCNQ1	ENST00000335475.6	c.96+4901A>G		intron_variant		1
KCNQ1	ENST00000496887.7	c.216+4901A>G		intron_variant		5
KCNQ1	ENST00000646564.2	c.477+4901A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122078 AN: 151978 Hom.: 49357 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.803 AC: 122183 AN: 152096 Hom.: 49407 Cov.: 33 AF XY: 0.807 AC XY: 60023 AN XY: 74348

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.804

Alfa AF: 0.811 Hom.: 6472

Bravo AF: 0.801

Asia WGS AF: 0.903 AC: 3138 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.67

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: rs179436; hg19: chr11-2554149;