rs1991808

chr10-76903955-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.3147+6011G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,978 control chromosomes in the GnomAD database, including 22,108 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 0.51 (22106 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.3147+6011G>A		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.457+1933C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.3147+6011G>A		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.425+1933C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78185 AN: 151856 Hom.: 22102 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.514 AC: 78188 AN: 151974 Hom.: 22106 Cov.: 32 AF XY: 0.511 AC XY: 37984 AN XY: 74288

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.544

Alfa AF: 0.575 Hom.: 3277

Bravo AF: 0.487

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.20

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: rs1991808; hg19: chr10-78663713;