chr11-2477948-G-A

Variant names:

• chr11-2477948-G-A
• rs757092
• NM_000218.3:c.386+32464G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000218.3(KCNQ1):​c.386+32464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,952 control chromosomes in the GnomAD database, including 22,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22351 hom., cov: 31)
• Consequence: KCNQ1 NM_000218.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140
• Publications: 15 publications found

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]

KCNQ1 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• long QT syndrome 1

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Jervell and Lange-Nielsen syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• atrial fibrillation, familial, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short QT syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• short QT syndrome type 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Jervell and Lange-Nielsen syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-2477948-G-A is Benign according to our data. Variant chr11-2477948-G-A is described in ClinVar as Benign. ClinVar VariationId is 1600312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000218.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	NM_000218.3	MANE Select	c.386+32464G>A		intron	N/A	NP_000209.2
	KCNQ1	NM_001406836.1		c.386+32464G>A		intron	N/A	NP_001393765.1
	KCNQ1	NM_001406837.1		c.24+32464G>A		intron	N/A	NP_001393766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.386+32464G>A		intron	N/A	ENSP00000155840.2
	KCNQ1	ENST00000335475.6	TSL:1	c.5+16234G>A		intron	N/A	ENSP00000334497.5
	KCNQ1	ENST00000345015.4	TSL:1	n.163+32464G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78924 AN: 151834 Hom.: 22335 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.520 AC: 78982 AN: 151952 Hom.: 22351 Cov.: 31 AF XY: 0.520 AC XY: 38646 AN XY: 74268

African (AFR) AF: 0.275 AC: 11381 AN: 41408

American (AMR) AF: 0.519 AC: 7933 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2174 AN: 3464

East Asian (EAS) AF: 0.599 AC: 3099 AN: 5172

South Asian (SAS) AF: 0.577 AC: 2771 AN: 4804

European-Finnish (FIN) AF: 0.632 AC: 6674 AN: 10560

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43055 AN: 67936

Other (OTH) AF: 0.552 AC: 1169 AN: 2116

Alfa AF: 0.508 Hom.: 12696

Bravo AF: 0.500

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs757092; hg19: chr11-2499178;