rs4766311

Variant names:

• chr12-4913272-C-T
• rs4766311
• NM_000217.3:c.*406C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-4913272-C-T
• chr12-4913272-C-A
• chr12-4913272-C-G

Variant summary

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

The NM_000217.3(KCNA1):​c.*406C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.47 in 268,744 control chromosomes in the GnomAD database, including 30,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18121 hom., cov: 33)
  • Exomes 𝑓: 0.45 (12171 hom.)
• Consequence: KCNA1 NM_000217.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.57
• Publications: 14 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Genomics England PanelApp, Orphanet
• episodic kinesigenic dyskinesia 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P
• isolated autosomal dominant hypomagnesemia, Glaudemans type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000256654 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-4913272-C-T is Benign according to our data. Variant chr12-4913272-C-T is described in ClinVar as Benign. ClinVar VariationId is 309154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNA1	NM_000217.3	MANE Select	c.*406C>T		3_prime_UTR	Exon 2 of 2	NP_000208.2	Q09470

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNA1	ENST00000382545.5	TSL:4 MANE Select	c.*406C>T		3_prime_UTR	Exon 2 of 2	ENSP00000371985.3	Q09470
	KCNA1	ENST00000639680.1	TSL:5	c.76-369C>T		intron	N/A	ENSP00000492218.1	A0A1W2PQM4
	KCNA1	ENST00000639306.1	TSL:5	n.*406C>T		non_coding_transcript_exon	Exon 1 of 2	ENSP00000492506.1	A0A1W2PRI2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73798 AN: 151888 Hom.: 18120 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.490

GnomAD4 exome AF: 0.450 AC: 52488 AN: 116738 Hom.: 12171 Cov.: 0 AF XY: 0.443 AC XY: 27265 AN XY: 61494

African (AFR) AF: 0.424 AC: 822 AN: 1940

American (AMR) AF: 0.520 AC: 2066 AN: 3972

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1095 AN: 2250

East Asian (EAS) AF: 0.555 AC: 2177 AN: 3922

South Asian (SAS) AF: 0.382 AC: 6376 AN: 16712

European-Finnish (FIN) AF: 0.465 AC: 9175 AN: 19736

Middle Eastern (MID) AF: 0.516 AC: 188 AN: 364

European-Non Finnish (NFE) AF: 0.450 AC: 28134 AN: 62570

Other (OTH) AF: 0.466 AC: 2455 AN: 5272

GnomAD4 genome AF: 0.486 AC: 73821 AN: 152006 Hom.: 18121 Cov.: 33 AF XY: 0.485 AC XY: 36040 AN XY: 74290

African (AFR) AF: 0.473 AC: 19610 AN: 41438

American (AMR) AF: 0.512 AC: 7831 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1841 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2981 AN: 5174

South Asian (SAS) AF: 0.427 AC: 2057 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4929 AN: 10526

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32924 AN: 67980

Other (OTH) AF: 0.493 AC: 1040 AN: 2110

Alfa AF: 0.489 Hom.: 32599

Bravo AF: 0.493

Asia WGS AF: 0.495 AC: 1717 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Episodic ataxia type 1 (1)
-	-	1	Myokymia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.3
DANN	Benign	0.60
PhyloP100		4.6
Mutation Taster		=99/1	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: rs4766311; hg19: chr12-5022438; COSMIC: COSV66837385;