Genetic Variant KCNMA1:c.809-26705G>A (chr10-77147753-C-T) – 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.809-26705G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,294 control chromosomes in the GnomAD database, including 57,650 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 0.87 ( 57616 hom., cov: 32)

Exomes 𝑓: 0.88 ( 34 hom. )

Consequence

KCNMA1
NM_001161352.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

3 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-AS2 (HGNC:51214): (KCNMA1 antisense RNA 2)

KCNMA1-AS2 links:

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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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2 link	c.809-26705G>A		intron_variant	Intron 5 of 27	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.809-26705G>A		intron_variant	Intron 5 of 27	1	NM_001161352.2	ENSP00000286628.8		Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132314

AN:

152086

Hom.:

57571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.914

Gnomad ASJ

AF:

0.885

Gnomad EAS

AF:

0.915

Gnomad SAS

AF:

0.864

Gnomad FIN

AF:

0.838

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.872

GnomAD4 exome

AF:

0.878

AC:

AN:

Hom.:

Cov.:

AF XY:

0.909

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.875

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.870

AC:

132415

AN:

152204

Hom.:

57616

Cov.:

AF XY:

0.871

AC XY:

64804

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.899

AC:

37348

AN:

41526

American (AMR)

AF:

0.915

AC:

13992

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.885

AC:

3071

AN:

3472

East Asian (EAS)

AF:

0.915

AC:

4738

AN:

5178

South Asian (SAS)

AF:

0.863

AC:

4159

AN:

4818

European-Finnish (FIN)

AF:

0.838

AC:

8885

AN:

10600

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.844

AC:

57413

AN:

67996

Other (OTH)

AF:

0.873

AC:

1843

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

870

1741

2611

3482

4352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.853

Hom.:

6744

Bravo

AF:

0.878

Asia WGS

AF:

0.879

AC:

3055

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.8

(source)

DANN

Benign

0.48

PhyloP100

0.038

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