rs11002137

Variant names:

• chr10-77364836-T-C
• rs11002137
• NM_001161352.2:c.540+39026A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.540+39026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,104 control chromosomes in the GnomAD database, including 5,396 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 0.24 (5396 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 7 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.540+39026A>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	c.540+39026A>G		intron_variant	Intron 2 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36005 AN: 151984 Hom.: 5394 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.237 AC: 36000 AN: 152104 Hom.: 5396 Cov.: 32 AF XY: 0.231 AC XY: 17166 AN XY: 74324

African (AFR) AF: 0.0761 AC: 3162 AN: 41526

American (AMR) AF: 0.190 AC: 2900 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3468

East Asian (EAS) AF: 0.159 AC: 821 AN: 5148

South Asian (SAS) AF: 0.126 AC: 606 AN: 4826

European-Finnish (FIN) AF: 0.272 AC: 2881 AN: 10584

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23595 AN: 67956

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.268 Hom.: 1392

Bravo AF: 0.223

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.77
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11002137; hg19: chr10-79124594;