10-77045387-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.1750-5750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,330 control chromosomes in the GnomAD database, including 65,709 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 0.93 (65709 hom., cov: 34)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763

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 (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.1750-5750T>C		intron_variant		ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.1750-5750T>C		intron_variant		1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141315 AN: 152212 Hom.: 65665 Cov.: 34

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.928 AC: 141418 AN: 152330 Hom.: 65709 Cov.: 34 AF XY: 0.928 AC XY: 69113 AN XY: 74480

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.967

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.935

Alfa AF: 0.926 Hom.: 8111

Bravo AF: 0.928

Asia WGS AF: 0.852 AC: 2965 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	8.7
Dann	Benign	0.45

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: rs1247766; hg19: chr10-78805145;