rs12762512

Variant names:

• chr10-76937839-T-C
• rs12762512
• NM_001161352.2:c.2902+6934A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.2902+6934A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 152,170 control chromosomes in the GnomAD database, including 782 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 0.074 (782 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161352.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.2902+6934A>G		intron	N/A	NP_001154824.1
	KCNMA1	NM_001437422.1		c.2860+6934A>G		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.2851+6934A>G		intron	N/A	NP_001154825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.2902+6934A>G		intron	N/A	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.2851+6934A>G		intron	N/A	ENSP00000485867.1
	KCNMA1	ENST00000639406.1	TSL:1	c.2737+6934A>G		intron	N/A	ENSP00000491732.1

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11302 AN: 152052 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0744 AC: 11321 AN: 152170 Hom.: 782 Cov.: 32 AF XY: 0.0733 AC XY: 5457 AN XY: 74406

African (AFR) AF: 0.181 AC: 7528 AN: 41496

American (AMR) AF: 0.0880 AC: 1344 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3466

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5178

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4820

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0205 AC: 1391 AN: 68000

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0412 Hom.: 350

Bravo AF: 0.0835

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.24
PhyloP100		0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12762512; hg19: chr10-78697597;