rs872794

Positions:

• chr10-77299725-T-C

Variant summary

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

The NM_001161352.2(KCNMA1):​c.541-48469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,896 control chromosomes in the GnomAD database, including 9,759 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 0.34 (9759 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.541-48469A>G		intron_variant		ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.541-48469A>G		intron_variant		1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52083 AN: 151780 Hom.: 9733 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.343 AC: 52154 AN: 151896 Hom.: 9759 Cov.: 32 AF XY: 0.345 AC XY: 25577 AN XY: 74204

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.357

Alfa AF: 0.286 Hom.: 8951

Bravo AF: 0.350

Asia WGS AF: 0.514 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.69

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: rs872794; hg19: chr10-79059483;