10-77164866-A-G

Position:

• chr10-77164866-A-G

Variant summary

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

The NM_001161352.2(KCNMA1):​c.808+18555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,020 control chromosomes in the GnomAD database, including 9,616 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 0.32 (9616 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.808+18555T>C		intron_variant		ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.808+18555T>C		intron_variant		1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48231 AN: 151902 Hom.: 9597 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.318 AC: 48267 AN: 152020 Hom.: 9616 Cov.: 32 AF XY: 0.332 AC XY: 24637 AN XY: 74270

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.333

Alfa AF: 0.332 Hom.: 12082

Bravo AF: 0.319

Asia WGS AF: 0.701 AC: 2431 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.044
DANN	Benign	0.34

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: rs527458; hg19: chr10-78924624;