Variant 1-40817249-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004700.4(KCNQ4):c.315-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,608,150 control chromosomes in the GnomAD database, including 17,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1925 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15728 hom. )

Consequence

KCNQ4
NM_004700.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.288

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:

KCNQ4 (HGNC:):

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=-0.83).

BP6

Variant 1-40817249-C-T is Benign according to our data. Variant chr1-40817249-C-T is described in ClinVar as [Benign]. Clinvar id is 259519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40817249-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ4	NM_004700.4 linkuse as main transcript	c.315-16C>T		intron_variant		ENST00000347132.10	NP_004691.2	P56696-1B3KQH8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KCNQ4	ENST00000347132.10 linkuse as main transcript	c.315-16C>T	intron_variant	1	NM_004700.4	ENSP00000262916.6	P56696-1
KCNQ4	ENST00000509682.6 linkuse as main transcript	c.315-16C>T	intron_variant	5		ENSP00000423756.2	P56696-2
KCNQ4	ENST00000443478.3 linkuse as main transcript	c.-17C>T	upstream_gene_variant	5		ENSP00000406735.3	H0Y6N7

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23666

AN:

152146

Hom.:

1919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.157

AC:

38664

AN:

246148

Hom.:

3231

AF XY:

0.157

AC XY:

20893

AN XY:

133082

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.310

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.144

AC:

209651

AN:

1455886

Hom.:

15728

Cov.:

AF XY:

0.144

AC XY:

104377

AN XY:

724158

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.275

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.156

AC:

23685

AN:

152264

Hom.:

1925

Cov.:

AF XY:

0.157

AC XY:

11704

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.143

Hom.:

302

Bravo

AF:

0.157

Asia WGS

AF:

0.236

AC:

819

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal dominant nonsyndromic hearing loss 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.0

DANN

Benign

0.28

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