rs11002137

Positions:

• chr10-77364836-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.540+39026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,104 control chromosomes in the GnomAD database, including 5,396 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 0.24 (5396 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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-AS3 (HGNC:51215): (KCNMA1 antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.540+39026A>G		intron_variant		ENST00000286628.14	NP_001154824.1
KCNMA1-AS3	NR_126365.1	n.810-8011T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.540+39026A>G		intron_variant		1	NM_001161352.2	ENSP00000286628	A2
KCNMA1-AS3	ENST00000418515.1	n.277-8011T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36005 AN: 151984 Hom.: 5394 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.237 AC: 36000 AN: 152104 Hom.: 5396 Cov.: 32 AF XY: 0.231 AC XY: 17166 AN XY: 74324

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.212

Alfa AF: 0.273 Hom.: 1388

Bravo AF: 0.223

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs11002137; hg19: chr10-79124594;