rs1897593

Variant names:

• chr10-76880150-A-C
• rs1897593
• ENST00000640807.1:c.3363-2257T>G

Variant summary

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

The ENST00000640807.1(KCNMA1):​c.3363-2257T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,166 control chromosomes in the GnomAD database, including 2,992 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 0.15 (2992 hom., cov: 33)
• Consequence: KCNMA1 ENST00000640807.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 2 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001322830.2	c.3615-2257T>G		intron_variant	Intron 30 of 30		NP_001309759.1
KCNMA1	NM_001322835.2	c.3606-2260T>G		intron_variant	Intron 29 of 29		NP_001309764.1
KCNMA1	NM_001437423.1	c.3600-2257T>G		intron_variant	Intron 28 of 28		NP_001424352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000640807.1	c.3363-2257T>G		intron_variant	Intron 27 of 27	1		ENSP00000491555.1
KCNMA1	ENST00000604624.6	c.3108-2257T>G		intron_variant	Intron 27 of 27	1		ENSP00000473714.2
KCNMA1	ENST00000639691.1	n.*2392-2260T>G		intron_variant	Intron 24 of 24	1		ENSP00000491040.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22111 AN: 152048 Hom.: 2968 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.146 AC: 22180 AN: 152166 Hom.: 2992 Cov.: 33 AF XY: 0.149 AC XY: 11060 AN XY: 74408

African (AFR) AF: 0.363 AC: 15046 AN: 41450

American (AMR) AF: 0.104 AC: 1588 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3472

East Asian (EAS) AF: 0.124 AC: 644 AN: 5188

South Asian (SAS) AF: 0.169 AC: 816 AN: 4818

European-Finnish (FIN) AF: 0.0671 AC: 712 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2910 AN: 68016

Other (OTH) AF: 0.118 AC: 250 AN: 2110

Alfa AF: 0.0705 Hom.: 1457

Bravo AF: 0.156

Asia WGS AF: 0.175 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1897593; hg19: chr10-78639908;