rs1897593

chr10-76880150-A-C

Variant summary

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

The ENST00000640807.1(KCNMA1):c.3363-2257T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,166 control chromosomes in the GnomAD database, including 2,992 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 0.15 (2992 hom., cov: 33)
• Consequence: KCNMA1 ENST00000640807.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001014797.3	c.3525-2257T>G		intron_variant
KCNMA1	NM_001271518.2	c.3363-2257T>G		intron_variant
KCNMA1	NM_001322829.2	c.3522-2260T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000604624.6	c.3108-2257T>G		intron_variant		1
KCNMA1	ENST00000640807.1	c.3363-2257T>G		intron_variant		1
KCNMA1	ENST00000639691.1	c.*2392-2260T>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22111 AN: 152048 Hom.: 2968 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.146 AC: 22180 AN: 152166 Hom.: 2992 Cov.: 33 AF XY: 0.149 AC XY: 11060 AN XY: 74408

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.0428

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0996 Hom.: 709

Bravo AF: 0.156

Asia WGS AF: 0.175 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1897593; hg19: chr10-78639908;