rs1131824

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_001161352.2(KCNMA1):c.687C>T(p.Phe229Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,600,698 control chromosomes in the GnomAD database, including 108,354 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15184 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93170 hom. )

Consequence

KCNMA1
NM_001161352.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.40

Publications

25 publications found

Variant links:

Genes affected

KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

KCNMA1 Gene-Disease associations (from GenCC):

generalized epilepsy-paroxysmal dyskinesia syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
Liang-Wang syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
cerebellar atrophy, developmental delay, and seizures
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

KCNMA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 10-77184832-G-A is Benign according to our data. Variant chr10-77184832-G-A is described in ClinVar as Benign. ClinVar VariationId is 129328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2 link	c.687C>T	p.Phe229Phe	synonymous_variant	Exon 4 of 28	ENST00000286628.14	NP_001154824.1	Q12791-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14 link	c.687C>T	p.Phe229Phe	synonymous_variant	Exon 4 of 28	1	NM_001161352.2	ENSP00000286628.8		Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64599

AN:

151846

Hom.:

15161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.383

GnomAD2 exomes

AF:

0.348

AC:

87164

AN:

250790

AF XY:

0.346

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.352

AC:

510383

AN:

1448734

Hom.:

93170

Cov.:

AF XY:

0.351

AC XY:

253401

AN XY:

721448

show subpopulations

African (AFR)

AF:

0.636

AC:

21078

AN:

33144

American (AMR)

AF:

0.213

AC:

9528

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

10564

AN:

26044

East Asian (EAS)

AF:

0.255

AC:

10087

AN:

39598

South Asian (SAS)

AF:

0.330

AC:

28340

AN:

85980

European-Finnish (FIN)

AF:

0.371

AC:

19778

AN:

53272

Middle Eastern (MID)

AF:

0.410

AC:

2352

AN:

5740

European-Non Finnish (NFE)

AF:

0.352

AC:

387281

AN:

1100358

Other (OTH)

AF:

0.357

AC:

21375

AN:

59904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

14698

29396

44093

58791

73489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12342

24684

37026

49368

61710

<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:

0.425

AC:

64660

AN:

151964

Hom.:

15184

Cov.:

AF XY:

0.423

AC XY:

31414

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.634

AC:

26273

AN:

41448

American (AMR)

AF:

0.324

AC:

4943

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1418

AN:

3466

East Asian (EAS)

AF:

0.260

AC:

1334

AN:

5124

South Asian (SAS)

AF:

0.333

AC:

1604

AN:

4814

European-Finnish (FIN)

AF:

0.386

AC:

4072

AN:

10550

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.351

AC:

23844

AN:

67984

Other (OTH)

AF:

0.379

AC:

799

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1789

3577

5366

7154

8943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.376

Hom.:

43685

Bravo

AF:

0.428

Asia WGS

AF:

0.313

AC:

1086

AN:

3478

EpiCase

AF:

0.355

EpiControl

AF:

0.359

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Generalized epilepsy-paroxysmal dyskinesia syndrome

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Feb 28, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Cerebellar atrophy, developmental delay, and seizures

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Liang-Wang syndrome

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

1.4

PromoterAI

-0.035

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over