10-76889844-T-C

Position:

• chr10-76889844-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161352.2(KCNMA1):​c.3343-275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 486,404 control chromosomes in the GnomAD database, including 135,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46544 hom., cov: 31)
  • Exomes 𝑓: 0.73 (89451 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-76889844-T-C is Benign according to our data. Variant chr10-76889844-T-C is described in ClinVar as [Benign]. Clinvar id is 1179300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.3343-275A>G		intron_variant		ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.3343-275A>G		intron_variant		1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118027 AN: 152008 Hom.: 46495 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.726 AC: 242550 AN: 334278 Hom.: 89451 AF XY: 0.717 AC XY: 128329 AN XY: 179004

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.674

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.747

GnomAD4 genome AF: 0.777 AC: 118133 AN: 152126 Hom.: 46544 Cov.: 31 AF XY: 0.773 AC XY: 57505 AN XY: 74354

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.780

Alfa AF: 0.760 Hom.: 58741

Bravo AF: 0.773

Asia WGS AF: 0.600 AC: 2084 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.036
DANN	Benign	0.52

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: rs2288839; hg19: chr10-78649602;