rs2361660

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004700.4(KCNQ4):c.708+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,581,178 control chromosomes in the GnomAD database, including 384,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33430 hom., cov: 32)

Exomes 𝑓: 0.70 ( 350707 hom. )

Consequence

KCNQ4
NM_004700.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0700

Variant links:

Genes affected

KCNQ4 (HGNC:6298): (potassium voltage-gated channel subfamily Q member 4) The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KCNQ4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-40818694-G-C is Benign according to our data. Variant chr1-40818694-G-C is described in ClinVar as [Benign]. Clinvar id is 45104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40818694-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ4	NM_004700.4 link	c.708+14G>C		intron_variant	Intron 4 of 13	ENST00000347132.10	NP_004691.2	P56696-1B3KQH8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNQ4	ENST00000347132.10 link	c.708+14G>C	intron_variant	Intron 4 of 13	1	NM_004700.4	ENSP00000262916.6	P56696-1
KCNQ4	ENST00000509682.6 link	c.708+14G>C	intron_variant	Intron 4 of 12	5		ENSP00000423756.2	P56696-2
KCNQ4	ENST00000443478.3 link	c.393+14G>C	intron_variant	Intron 3 of 12	5		ENSP00000406735.3	H0Y6N7

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99842

AN:

151884

Hom.:

33414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.761

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.730

Gnomad OTH

AF:

0.661

GnomAD3 exomes

AF:

0.643

AC:

124402

AN:

193618

Hom.:

40583

AF XY:

0.647

AC XY:

69581

AN XY:

107580

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.519

Gnomad ASJ exome

AF:

0.670

Gnomad EAS exome

AF:

0.468

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.720

Gnomad NFE exome

AF:

0.727

Gnomad OTH exome

AF:

0.669

GnomAD4 exome

AF:

0.697

AC:

995938

AN:

1429174

Hom.:

350707

Cov.:

AF XY:

0.694

AC XY:

492785

AN XY:

709718

show subpopulations

Gnomad4 AFR exome

AF:

0.591

Gnomad4 AMR exome

AF:

0.525

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.415

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.734

Gnomad4 NFE exome

AF:

0.726

Gnomad4 OTH exome

AF:

0.679

GnomAD4 genome

AF:

0.657

AC:

99896

AN:

152004

Hom.:

33430

Cov.:

AF XY:

0.653

AC XY:

48467

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.592

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.669

Gnomad4 EAS

AF:

0.454

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.716

Gnomad4 NFE

AF:

0.730

Gnomad4 OTH

AF:

0.664

Alfa

AF:

0.703

Hom.:

6966

Bravo

AF:

0.642

Asia WGS

AF:

0.540

AC:

1880

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

708+14G>C in Intron 04 of KCNQ4: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 39.7% (1449/3654) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs2361660). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 2A

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.7

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over