rs1907724

chr10-76980090-G-Achr10-76980090-G-Cchr10-76980090-G-T

Variant summary

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

The NM_001161352.2(KCNMA1):c.2267-10023C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,006 control chromosomes in the GnomAD database, including 43,986 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 0.76 (43985 hom., cov: 32)
  • Exomes 𝑓: 0.63 (1 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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]

KCNMA1-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.2267-10023C>T		intron_variant		ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2267-10023C>T		intron_variant		1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115249 AN: 151880 Hom.: 43951 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.759 AC: 115336 AN: 151998 Hom.: 43985 Cov.: 32 AF XY: 0.763 AC XY: 56652 AN XY: 74256

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.747

Alfa AF: 0.758 Hom.: 43745

Bravo AF: 0.755

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.9
Dann	Benign	0.61

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: rs1907724; hg19: chr10-78739848;