rs2131218

Positions:

• chr10-76935207-G-A

Variant summary

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

The NM_001161352.2(KCNMA1):​c.2902+9566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,122 control chromosomes in the GnomAD database, including 7,608 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 0.27 (7608 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.2902+9566C>T		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.457+33185G>A		intron_variant, non_coding_transcript_variant
LOC124902466	XR_007062207.1	n.275-4471G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2902+9566C>T		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.425+33185G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41316 AN: 152004 Hom.: 7598 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.272 AC: 41372 AN: 152122 Hom.: 7608 Cov.: 33 AF XY: 0.267 AC XY: 19862 AN XY: 74374

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.218

Alfa AF: 0.179 Hom.: 3802

Bravo AF: 0.287

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.51

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: rs2131218; hg19: chr10-78694965;