NM_001161352.2:c.809-23142A>G

Variant names:

• chr10-77144190-T-C
• rs993609
• NM_001161352.2:c.809-23142A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.809-23142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,026 control chromosomes in the GnomAD database, including 15,182 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 0.44 (15182 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.809-23142A>G		intron_variant	Intron 5 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.809-23142A>G		intron_variant	Intron 5 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66327 AN: 151910 Hom.: 15177 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.436 AC: 66353 AN: 152026 Hom.: 15182 Cov.: 33 AF XY: 0.428 AC XY: 31789 AN XY: 74306

African (AFR) AF: 0.430 AC: 17828 AN: 41472

American (AMR) AF: 0.350 AC: 5339 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.0392 AC: 203 AN: 5172

South Asian (SAS) AF: 0.320 AC: 1543 AN: 4818

European-Finnish (FIN) AF: 0.461 AC: 4875 AN: 10566

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33336 AN: 67944

Other (OTH) AF: 0.440 AC: 929 AN: 2112

Alfa AF: 0.463 Hom.: 2146

Bravo AF: 0.428

Asia WGS AF: 0.191 AC: 663 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.72
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs993609; hg19: chr10-78903948;