rs1356090

Variant names:

• chr10-77635554-T-C
• rs1356090
• ENST00000480683.2:c.*833A>G

Variant summary

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

The ENST00000480683.2(KCNMA1):​c.*833A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,986 control chromosomes in the GnomAD database, including 3,107 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 0.18 (3106 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: KCNMA1 ENST00000480683.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 3 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)

ENSG00000293869 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000480683.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.378+1711A>G		intron	N/A	NP_001154824.1
	KCNMA1	NM_001271522.2		c.*833A>G		3_prime_UTR	Exon 2 of 2	NP_001258451.1
	KCNMA1	NM_001437422.1		c.378+1711A>G		intron	N/A	NP_001424351.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000480683.2	TSL:1	c.*833A>G		3_prime_UTR	Exon 2 of 2	ENSP00000474686.1
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.378+1711A>G		intron	N/A	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.378+1711A>G		intron	N/A	ENSP00000485867.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27491 AN: 151784 Hom.: 3102 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.214 AC: 18 AN: 84 Hom.: 1 Cov.: 0 AF XY: 0.183 AC XY: 11 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.226 AC: 14 AN: 62

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.181 AC: 27501 AN: 151902 Hom.: 3106 Cov.: 32 AF XY: 0.184 AC XY: 13678 AN XY: 74228

African (AFR) AF: 0.121 AC: 5033 AN: 41424

American (AMR) AF: 0.169 AC: 2574 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2782 AN: 5152

South Asian (SAS) AF: 0.326 AC: 1568 AN: 4808

European-Finnish (FIN) AF: 0.186 AC: 1960 AN: 10560

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12281 AN: 67914

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.174 Hom.: 309

Bravo AF: 0.176

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.13
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: rs1356090; hg19: chr10-79395312;