10-77017710-C-T

Variant names:

• chr10-77017710-C-T
• rs10509379
• NM_001161352.2:c.2015+1303G>A

Variant summary

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

The NM_001161352.2(KCNMA1):​c.2015+1303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,092 control chromosomes in the GnomAD database, including 4,101 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 0.20 (4101 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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]

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 (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.2015+1303G>A		intron_variant	Intron 17 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2015+1303G>A		intron_variant	Intron 17 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30385 AN: 151976 Hom.: 4102 Cov.: 32

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.200 AC: 30376 AN: 152092 Hom.: 4101 Cov.: 32 AF XY: 0.196 AC XY: 14565 AN XY: 74330

Gnomad4 AFR AF: 0.0486

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.214

Alfa AF: 0.241 Hom.: 2536

Bravo AF: 0.183

Asia WGS AF: 0.0450 AC: 159 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	0.49
DANN	Benign	0.58

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: rs10509379; hg19: chr10-78777468;