dbSNP rs35773: KCNMA1:c.540+29887A>G (chr10-77373975-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001161352.2(KCNMA1):c.540+29887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,216 control chromosomes in the GnomAD database, including 50,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.81 ( 50287 hom., cov: 32)

Exomes 𝑓: 0.82 ( 28 hom. )

Consequence

KCNMA1
NM_001161352.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.81

Publications

4 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 links:

KCNMA1-AS3 (HGNC:51215): (KCNMA1 antisense RNA 3)

KCNMA1-AS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2 link	c.540+29887A>G		intron_variant	Intron 2 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14 link	c.540+29887A>G		intron_variant	Intron 2 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes

AF:

0.811

AC:

123337

AN:

152016

Hom.:

50234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.914

Gnomad AMR

AF:

0.788

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.724

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.801

Gnomad OTH

AF:

0.815

GnomAD4 exome

AF:

0.817

AC:

AN:

Hom.:

AF XY:

0.814

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.813

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.811

AC:

123447

AN:

152134

Hom.:

50287

Cov.:

AF XY:

0.804

AC XY:

59817

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.875

AC:

36341

AN:

41520

American (AMR)

AF:

0.789

AC:

12064

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.895

AC:

3105

AN:

3470

East Asian (EAS)

AF:

0.639

AC:

3296

AN:

5156

South Asian (SAS)

AF:

0.723

AC:

3475

AN:

4804

European-Finnish (FIN)

AF:

0.745

AC:

7887

AN:

10588

Middle Eastern (MID)

AF:

0.881

AC:

259

AN:

294

European-Non Finnish (NFE)

AF:

0.801

AC:

54466

AN:

67982

Other (OTH)

AF:

0.815

AC:

1722

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1214

2428

3642

4856

6070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.804

Hom.:

6359

Bravo

AF:

0.816

Asia WGS

AF:

0.730

AC:

2537

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0030

(source)

DANN

Benign

0.51

PhyloP100

-3.8

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

Computational scores

Splicing

Publications

Other links and lift over