rs1247755

chr10-77037912-C-Gchr10-77037912-C-T

Variant summary

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

The NM_001161352.2(KCNMA1):c.1859+1616G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,994 control chromosomes in the GnomAD database, including 37,323 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 0.70 (37323 hom., cov: 31)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.1859+1616G>C		intron_variant		ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.1859+1616G>C		intron_variant		1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106438 AN: 151876 Hom.: 37285 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.701 AC: 106533 AN: 151994 Hom.: 37323 Cov.: 31 AF XY: 0.701 AC XY: 52094 AN XY: 74284

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.702

Alfa AF: 0.693 Hom.: 4560

Bravo AF: 0.706

Asia WGS AF: 0.748 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	15
Dann	Benign	0.77

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: rs1247755; hg19: chr10-78797670;