10-76889641-C-T

Position:

• chr10-76889641-C-T

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.3343-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,233,774 control chromosomes in the GnomAD database, including 275,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31875 hom., cov: 32)
  • Exomes 𝑓: 0.67 (243364 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.773

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=-0.84).
• BP6: Variant 10-76889641-C-T is Benign according to our data. Variant chr10-76889641-C-T is described in ClinVar as [Benign]. Clinvar id is 1221813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.3343-72G>A		intron_variant		ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.3343-72G>A		intron_variant		1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97635 AN: 151908 Hom.: 31837 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.667 AC: 721253 AN: 1081748 Hom.: 243364 Cov.: 15 AF XY: 0.662 AC XY: 368505 AN XY: 556420

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.643 AC: 97720 AN: 152026 Hom.: 31875 Cov.: 32 AF XY: 0.641 AC XY: 47625 AN XY: 74304

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.653

Alfa AF: 0.673 Hom.: 32938

Bravo AF: 0.630

Asia WGS AF: 0.544 AC: 1890 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	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.64

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: rs2288840; hg19: chr10-78649399;