rs2719995

chr10-77562344-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001161352.2(KCNMA1):c.378+74921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,006 control chromosomes in the GnomAD database, including 12,503 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 0.39 (12503 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.378+74921G>A		intron_variant		ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.378+74921G>A		intron_variant		1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59226 AN: 151888 Hom.: 12490 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.390 AC: 59247 AN: 152006 Hom.: 12503 Cov.: 33 AF XY: 0.388 AC XY: 28855 AN XY: 74296

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.392

Alfa AF: 0.439 Hom.: 6718

Bravo AF: 0.379

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	14
Dann	Benign	0.80

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: rs2719995; hg19: chr10-79322102;