rs7907270

Positions:

• chr10-77121185-A-G

Variant summary

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

The ENST00000286628.14(KCNMA1):​c.809-137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 686,138 control chromosomes in the GnomAD database, including 48,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11157 hom., cov: 32)
  • Exomes 𝑓: 0.36 (37159 hom.)
• Consequence: KCNMA1 ENST00000286628.14 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-77121185-A-G is Benign according to our data. Variant chr10-77121185-A-G is described in ClinVar as [Benign]. Clinvar id is 1250074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.809-137T>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.809-137T>C		intron_variant		1	NM_001161352.2	ENSP00000286628	A2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56519 AN: 151988 Hom.: 11144 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.357 AC: 190421 AN: 534032 Hom.: 37159 AF XY: 0.359 AC XY: 103776 AN XY: 288966

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.0175

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.372 AC: 56566 AN: 152106 Hom.: 11157 Cov.: 32 AF XY: 0.364 AC XY: 27105 AN XY: 74366

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.388

Alfa AF: 0.386 Hom.: 16328

Bravo AF: 0.367

Asia WGS AF: 0.171 AC: 595 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 05, 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	-0.71
CADD	Benign	12
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: rs7907270; hg19: chr10-78880943;