rs592676

chr10-77294199-T-A

Variant summary

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

The NM_001161352.2(KCNMA1):c.541-42943A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,158 control chromosomes in the GnomAD database, including 18,091 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 0.47 (18091 hom., cov: 34)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.541-42943A>T		intron_variant		ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.541-42943A>T		intron_variant		1	NM_001161352.2	A2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71346 AN: 152038 Hom.: 18084 Cov.: 34

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.469 AC: 71382 AN: 152158 Hom.: 18091 Cov.: 34 AF XY: 0.464 AC XY: 34479 AN XY: 74382

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.463

Alfa AF: 0.509 Hom.: 2511

Bravo AF: 0.458

Asia WGS AF: 0.220 AC: 762 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.44

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: rs592676; hg19: chr10-79053957;