rs542007

Positions:

• chr10-77246160-A-C
• chr10-77246160-A-G
• chr10-77246160-A-T

Variant summary

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

The ENST00000286628.14(KCNMA1):​c.602+5035T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,132 control chromosomes in the GnomAD database, including 34,581 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 0.67 (34581 hom., cov: 33)
• Consequence: KCNMA1 ENST00000286628.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.602+5035T>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.602+5035T>G		intron_variant		1	NM_001161352.2	ENSP00000286628	A2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102296 AN: 152014 Hom.: 34561 Cov.: 33

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.673 AC: 102371 AN: 152132 Hom.: 34581 Cov.: 33 AF XY: 0.671 AC XY: 49905 AN XY: 74352

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.687

Alfa AF: 0.667 Hom.: 26869

Bravo AF: 0.683

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.83

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: rs542007; hg19: chr10-79005918;