dbSNP rs16934131: KCNMA1:c.2267-7770A>G (chr10-76977837-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.2267-7770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 570,690 control chromosomes in the GnomAD database, including 18,017 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 0.23 ( 4308 hom., cov: 32)

Exomes 𝑓: 0.24 ( 13709 hom. )

Consequence

KCNMA1
NM_001161352.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.546

Publications

11 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-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

KCNMA1-AS1 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2 link	c.2267-7770A>G		intron_variant	Intron 19 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.2267-7770A>G		intron_variant	Intron 19 of 27	1	NM_001161352.2	ENSP00000286628.8		Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34593

AN:

151928

Hom.:

4312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.242

AC:

101487

AN:

418644

Hom.:

13709

Cov.:

AF XY:

0.244

AC XY:

53581

AN XY:

219834

show subpopulations

African (AFR)

AF:

0.168

AC:

2004

AN:

11932

American (AMR)

AF:

0.148

AC:

2622

AN:

17678

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

2381

AN:

13080

East Asian (EAS)

AF:

0.0233

AC:

688

AN:

29582

South Asian (SAS)

AF:

0.259

AC:

10375

AN:

40130

European-Finnish (FIN)

AF:

0.342

AC:

9413

AN:

27556

Middle Eastern (MID)

AF:

0.239

AC:

449

AN:

1878

European-Non Finnish (NFE)

AF:

0.268

AC:

67670

AN:

252226

Other (OTH)

AF:

0.239

AC:

5885

AN:

24582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3383

6766

10150

13533

16916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.228

AC:

34593

AN:

152046

Hom.:

4308

Cov.:

AF XY:

0.229

AC XY:

16987

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.166

AC:

6865

AN:

41474

American (AMR)

AF:

0.186

AC:

2835

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3468

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5178

South Asian (SAS)

AF:

0.257

AC:

1240

AN:

4824

European-Finnish (FIN)

AF:

0.359

AC:

3787

AN:

10548

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18120

AN:

67974

Other (OTH)

AF:

0.216

AC:

456

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1337

2673

4010

5346

6683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.246

Hom.:

18306

Bravo

AF:

0.208

Asia WGS

AF:

0.150

AC:

524

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.1

(source)

DANN

Benign

0.66

PhyloP100

0.55

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