rs11002212

Positions:

• chr10-77588977-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.378+48288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,286 control chromosomes in the GnomAD database, including 3,130 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 0.18 (3130 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.378+48288T>C		intron_variant		ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.378+48288T>C		intron_variant		1	NM_001161352.2	ENSP00000286628	A2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27806 AN: 152168 Hom.: 3119 Cov.: 33

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.183 AC: 27835 AN: 152286 Hom.: 3130 Cov.: 33 AF XY: 0.181 AC XY: 13449 AN XY: 74456

Gnomad4 AFR AF: 0.0522

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.225

Alfa AF: 0.244 Hom.: 5643

Bravo AF: 0.182

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs11002212; hg19: chr10-79348735;