10-76933202-C-G

Variant summary

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

The NM_001161352.2(KCNMA1):c.2902+11571G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,184 control chromosomes in the GnomAD database, including 514 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 0.059 (514 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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:51213): (KCNMA1 antisense RNA 1)

LOC124902466 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.2902+11571G>C		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.457+31180C>G		intron_variant, non_coding_transcript_variant
LOC124902466	XR_007062207.1	n.274+2965C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2902+11571G>C		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.425+31180C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8946 AN: 152066 Hom.: 509 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0589 AC: 8963 AN: 152184 Hom.: 514 Cov.: 33 AF XY: 0.0571 AC XY: 4250 AN XY: 74390

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0753

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.0644

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.00836 Hom.: 2

Bravo AF: 0.0672

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.4
Dann	Benign	0.57

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: rs1907732; hg19: chr10-78692960;