dbSNP rs1877993: KCNMA1:c.378+23576G>A (chr10-77613689-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.378+23576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,082 control chromosomes in the GnomAD database, including 20,594 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 0.51 ( 20594 hom., cov: 33)

Consequence

KCNMA1
NM_001161352.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.877

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 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:

ENSG00000306833 (HGNC:):

ENSG00000306833 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=-0.57).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2 link	c.378+23576G>A		intron_variant	Intron 1 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.378+23576G>A		intron_variant	Intron 1 of 27	1	NM_001161352.2	ENSP00000286628.8		Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78151

AN:

151964

Hom.:

20559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.514

AC:

78231

AN:

152082

Hom.:

20594

Cov.:

AF XY:

0.508

AC XY:

37761

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.593

AC:

24590

AN:

41500

American (AMR)

AF:

0.558

AC:

8522

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1856

AN:

3468

East Asian (EAS)

AF:

0.211

AC:

1091

AN:

5178

South Asian (SAS)

AF:

0.338

AC:

1630

AN:

4822

European-Finnish (FIN)

AF:

0.451

AC:

4764

AN:

10570

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.501

AC:

34052

AN:

67952

Other (OTH)

AF:

0.523

AC:

1100

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1941

3883

5824

7766

9707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.510

Hom.:

19975

Bravo

AF:

0.527

Asia WGS

AF:

0.309

AC:

1075

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.7

(source)

DANN

Benign

0.80

PhyloP100

0.88

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over