rs1356090

Positions:

• chr10-77635554-T-C

Variant summary

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

The ENST00000480683.2(KCNMA1):​c.*833A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,986 control chromosomes in the GnomAD database, including 3,107 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 (3106 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: KCNMA1 ENST00000480683.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.378+1711A>G		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+1711A>G		intron_variant		1	NM_001161352.2	ENSP00000286628	A2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27491 AN: 151784 Hom.: 3102 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.214 AC: 18 AN: 84 Hom.: 1 Cov.: 0 AF XY: 0.183 AC XY: 11 AN XY: 60

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.181 AC: 27501 AN: 151902 Hom.: 3106 Cov.: 32 AF XY: 0.184 AC XY: 13678 AN XY: 74228

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.182

Alfa AF: 0.176 Hom.: 304

Bravo AF: 0.176

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.54

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: rs1356090; hg19: chr10-79395312;