rs4766309

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000217.3(KCNA1):c.1440T>A(p.Thr480Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,613,506 control chromosomes in the GnomAD database, including 400,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43764 hom., cov: 31)

Exomes 𝑓: 0.70 ( 357053 hom. )

Consequence

KCNA1
NM_000217.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.46

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

episodic ataxia type 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
episodic kinesigenic dyskinesia 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated autosomal dominant hypomagnesemia, Glaudemans type
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

KCNA1 links:

ENSG00000256654 (HGNC:):

ENSG00000256654 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 12-4912818-T-A is Benign according to our data. Variant chr12-4912818-T-A is described in ClinVar as Benign. ClinVar VariationId is 129313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000217.3. 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
	KCNA1	NM_000217.3	MANE Select	c.1440T>A	p.Thr480Thr	synonymous	Exon 2 of 2	NP_000208.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNA1	ENST00000382545.5	TSL:4 MANE Select	c.1440T>A	p.Thr480Thr	synonymous	Exon 2 of 2	ENSP00000371985.3
KCNA1	ENST00000639306.1	TSL:5	n.1278T>A		non_coding_transcript_exon	Exon 1 of 2	ENSP00000492506.1
KCNA1	ENST00000639680.1	TSL:5	c.75+552T>A		intron	N/A	ENSP00000492218.1

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

114409

AN:

152002

Hom.:

43710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.855

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.961

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.738

AC:

185521

AN:

251334

AF XY:

0.733

show subpopulations

Gnomad AFR exome

AF:

0.858

Gnomad AMR exome

AF:

0.756

Gnomad ASJ exome

AF:

0.690

Gnomad EAS exome

AF:

0.965

Gnomad FIN exome

AF:

0.761

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.719

GnomAD4 exome

AF:

0.696

AC:

1017485

AN:

1461386

Hom.:

357053

Cov.:

AF XY:

0.696

AC XY:

506360

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.861

AC:

28824

AN:

33472

American (AMR)

AF:

0.754

AC:

33708

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

18030

AN:

26132

East Asian (EAS)

AF:

0.951

AC:

37746

AN:

39700

South Asian (SAS)

AF:

0.730

AC:

62959

AN:

86250

European-Finnish (FIN)

AF:

0.758

AC:

40453

AN:

53398

Middle Eastern (MID)

AF:

0.771

AC:

4445

AN:

5768

European-Non Finnish (NFE)

AF:

0.673

AC:

747825

AN:

1111562

Other (OTH)

AF:

0.720

AC:

43495

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

16344

32688

49031

65375

81719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19400

38800

58200

77600

97000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.753

AC:

114520

AN:

152120

Hom.:

43764

Cov.:

AF XY:

0.759

AC XY:

56479

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.855

AC:

35475

AN:

41504

American (AMR)

AF:

0.750

AC:

11466

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.681

AC:

2363

AN:

3468

East Asian (EAS)

AF:

0.961

AC:

4975

AN:

5176

South Asian (SAS)

AF:

0.747

AC:

3595

AN:

4814

European-Finnish (FIN)

AF:

0.770

AC:

8144

AN:

10582

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.678

AC:

46117

AN:

67972

Other (OTH)

AF:

0.747

AC:

1575

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1422

2844

4265

5687

7109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.697

Hom.:

12114

Bravo

AF:

0.760

Asia WGS

AF:

0.867

AC:

3014

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.687

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Episodic ataxia type 1 (5)

not specified (4)

not provided (3)

Myokymia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.4

(source)

DANN

Benign

0.69

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over