NM_001161352.2:c.379-19371C>G

Variant names:

• chr10-77423394-G-C
• rs3862501
• NM_001161352.2:c.379-19371C>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.379-19371C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,026 control chromosomes in the GnomAD database, including 2,880 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 0.17 (2880 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 5 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 Gene-Disease associations (from GenCC):

• generalized epilepsy-paroxysmal dyskinesia syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• Liang-Wang syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• cerebellar atrophy, developmental delay, and seizures

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000295562 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.379-19371C>G		intron_variant	Intron 1 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.379-19371C>G		intron_variant	Intron 1 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26109 AN: 151908 Hom.: 2881 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.172 AC: 26142 AN: 152026 Hom.: 2880 Cov.: 33 AF XY: 0.166 AC XY: 12359 AN XY: 74320

African (AFR) AF: 0.312 AC: 12926 AN: 41412

American (AMR) AF: 0.195 AC: 2973 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3464

East Asian (EAS) AF: 0.0552 AC: 285 AN: 5164

South Asian (SAS) AF: 0.0739 AC: 356 AN: 4820

European-Finnish (FIN) AF: 0.0510 AC: 540 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8202 AN: 67992

Other (OTH) AF: 0.175 AC: 368 AN: 2106

Alfa AF: 0.150 Hom.: 285

Bravo AF: 0.193

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		-0.093
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: rs3862501; hg19: chr10-79183152;