rs16934131

Positions:

• chr10-76977837-T-C

Variant summary

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

The NM_001161352.2(KCNMA1):​c.2267-7770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 570,690 control chromosomes in the GnomAD database, including 18,017 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 0.23 (4308 hom., cov: 32)
  • Exomes 𝑓: 0.24 (13709 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.2267-7770A>G		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.652+33T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2267-7770A>G		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.620+33T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34593 AN: 151928 Hom.: 4312 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.242 AC: 101487 AN: 418644 Hom.: 13709 Cov.: 0 AF XY: 0.244 AC XY: 53581 AN XY: 219834

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.0233

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.228 AC: 34593 AN: 152046 Hom.: 4308 Cov.: 32 AF XY: 0.229 AC XY: 16987 AN XY: 74302

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.216

Alfa AF: 0.249 Hom.: 8228

Bravo AF: 0.208

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.1
DANN	Benign	0.66

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: rs16934131; hg19: chr10-78737595;