rs1991808

Variant names:

• chr10-76903955-C-T
• rs1991808
• ENST00000429850.2:n.2390C>T

Variant summary

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

The ENST00000429850.2(KCNMA1-AS1):​n.2390C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,978 control chromosomes in the GnomAD database, including 22,108 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 0.51 (22106 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: KCNMA1-AS1 ENST00000429850.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 2 publications found

Genes affected

KCNMA1-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429850.2. 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.3147+6011G>A		intron	N/A	NP_001154824.1
	KCNMA1	NM_001437422.1		c.3105+6011G>A		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.3096+6011G>A		intron	N/A	NP_001154825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1-AS1	ENST00000429850.2	TSL:1	n.2390C>T		non_coding_transcript_exon	Exon 2 of 2
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.3147+6011G>A		intron	N/A	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.3096+6011G>A		intron	N/A	ENSP00000485867.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78185 AN: 151856 Hom.: 22102 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.514 AC: 78188 AN: 151974 Hom.: 22106 Cov.: 32 AF XY: 0.511 AC XY: 37984 AN XY: 74288

African (AFR) AF: 0.287 AC: 11898 AN: 41448

American (AMR) AF: 0.466 AC: 7118 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2022 AN: 5162

South Asian (SAS) AF: 0.436 AC: 2097 AN: 4812

European-Finnish (FIN) AF: 0.690 AC: 7288 AN: 10562

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.643 AC: 43702 AN: 67942

Other (OTH) AF: 0.544 AC: 1149 AN: 2112

Alfa AF: 0.565 Hom.: 3320

Bravo AF: 0.487

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.20
PhyloP100		-0.22
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: rs1991808; hg19: chr10-78663713;