10-77148209-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.809-27161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,168 control chromosomes in the GnomAD database, including 57,624 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 0.87 (57624 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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-AS2 (HGNC:51214): (KCNMA1 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.809-27161G>A		intron_variant		ENST00000286628.14
KCNMA1-AS2	NR_120654.1	n.185+391C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.809-27161G>A		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS2	ENST00000428936.5	n.167+391C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132312 AN: 152050 Hom.: 57578 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.872

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.870 AC: 132414 AN: 152168 Hom.: 57624 Cov.: 32 AF XY: 0.871 AC XY: 64796 AN XY: 74388

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.874

Alfa AF: 0.862 Hom.: 8910

Bravo AF: 0.878

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.23
Dann	Benign	0.73

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: rs1903894; hg19: chr10-78907967;