rs4766310

Positions:

chr12-4912875-G-A

Variant summary

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

The NM_000217.3(KCNA1):c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,596,498 control chromosomes in the GnomAD database, including 182,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16131 hom., cov: 32)

Exomes 𝑓: 0.48 ( 166778 hom. )

Consequence

KCNA1
NM_000217.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.0550

Variant links:

Genes affected

KCNA1 (HGNC:6218): (potassium voltage-gated channel subfamily A member 1) This gene encodes a voltage-gated delayed potassium channel that is phylogenetically related to the Drosophila Shaker channel. The encoded protein has six putative transmembrane segments (S1-S6), and the loop between S5 and S6 forms the pore and contains the conserved selectivity filter motif (GYGD). The functional channel is a homotetramer. The N-terminus of the channel is associated with beta subunits that can modify the inactivation properties of the channel as well as affect expression levels. The C-terminus of the channel is complexed to a PDZ domain protein that is responsible for channel targeting. Mutations in this gene have been associated with myokymia with periodic ataxia (AEMK). [provided by RefSeq, Jul 2008]

KCNA1 links:

(HGNC:):

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=-0.95).

BP6

Variant 12-4912875-G-A is Benign according to our data. Variant chr12-4912875-G-A is described in ClinVar as [Benign]. Clinvar id is 195043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-4912875-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA1	NM_000217.3 linkuse as main transcript	c.*9G>A		3_prime_UTR_variant	2/2	ENST00000382545.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA1	ENST00000382545.5 linkuse as main transcript	c.*9G>A		3_prime_UTR_variant	2/2	4	NM_000217.3	P1
	ENST00000640877.1 linkuse as main transcript	n.606+2403G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69220

AN:

151876

Hom.:

16127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.480

AC:

120295

AN:

250746

Hom.:

29210

AF XY:

0.478

AC XY:

64862

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.587

Gnomad SAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.450

Gnomad NFE exome

AF:

0.480

Gnomad OTH exome

AF:

0.488

GnomAD4 exome

AF:

0.478

AC:

690181

AN:

1444504

Hom.:

166778

Cov.:

AF XY:

0.476

AC XY:

342886

AN XY:

719802

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.521

Gnomad4 ASJ exome

AF:

0.537

Gnomad4 EAS exome

AF:

0.580

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.479

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.456

AC:

69241

AN:

151994

Hom.:

16131

Cov.:

AF XY:

0.456

AC XY:

33895

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.530

Gnomad4 EAS

AF:

0.580

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.480

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.482

Hom.:

27116

Bravo

AF:

0.461

Asia WGS

AF:

0.494

AC:

1716

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 60. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2014	- -

Episodic ataxia type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 26, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

Myokymia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.0

DANN

Benign

0.58

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