11-2848935-A-G

Variant names:

• chr11-2848935-A-G
• rs10798
• NM_000218.3:c.*932A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000218.3(KCNQ1):​c.*932A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 453,978 control chromosomes in the GnomAD database, including 38,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12221 hom., cov: 34)
  • Exomes 𝑓: 0.39 (25979 hom.)
• Consequence: KCNQ1 NM_000218.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.06
• Publications: 27 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-AS1 (HGNC:42790): (KCNQ1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-2848935-A-G is Benign according to our data. Variant chr11-2848935-A-G is described in ClinVar as [Benign]. Clinvar id is 304268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ1	NM_000218.3	c.*932A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000155840.12	NP_000209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ1	ENST00000155840.12	c.*932A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_000218.3	ENSP00000155840.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58641 AN: 152064 Hom.: 12212 Cov.: 34

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.403

GnomAD2 exomes AF: 0.445 AC: 58052 AN: 130500 AF XY: 0.440

Gnomad AFR exome AF: 0.414

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.872

Gnomad FIN exome AF: 0.368

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.394 AC: 118970 AN: 301796 Hom.: 25979 Cov.: 0 AF XY: 0.400 AC XY: 68735 AN XY: 171996

African (AFR) AF: 0.409 AC: 3496 AN: 8554

American (AMR) AF: 0.552 AC: 15051 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 4109 AN: 10786

East Asian (EAS) AF: 0.870 AC: 8009 AN: 9210

South Asian (SAS) AF: 0.478 AC: 28516 AN: 59650

European-Finnish (FIN) AF: 0.367 AC: 4541 AN: 12368

Middle Eastern (MID) AF: 0.390 AC: 449 AN: 1150

European-Non Finnish (NFE) AF: 0.311 AC: 49407 AN: 158762

Other (OTH) AF: 0.384 AC: 5392 AN: 14042

GnomAD4 genome AF: 0.386 AC: 58693 AN: 152182 Hom.: 12221 Cov.: 34 AF XY: 0.394 AC XY: 29304 AN XY: 74404

African (AFR) AF: 0.405 AC: 16826 AN: 41498

American (AMR) AF: 0.473 AC: 7239 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3466

East Asian (EAS) AF: 0.859 AC: 4440 AN: 5170

South Asian (SAS) AF: 0.492 AC: 2376 AN: 4830

European-Finnish (FIN) AF: 0.372 AC: 3940 AN: 10592

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21248 AN: 68016

Other (OTH) AF: 0.404 AC: 855 AN: 2114

Alfa AF: 0.346 Hom.: 16930

Bravo AF: 0.396

Asia WGS AF: 0.632 AC: 2193 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27531917, 22199116) -

Long QT syndrome 1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Atrial fibrillation, familial, 3 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Jervell and Lange-Nielsen syndrome 1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Short QT syndrome type 2 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Congenital long QT syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.51
DANN	Benign	0.70
PhyloP100		-2.1
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: rs10798; hg19: chr11-2870165;