rs12762512

Positions:

• chr10-76937839-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.2902+6934A>G		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.457+35817T>C		intron_variant, non_coding_transcript_variant
LOC124902466	XR_007062207.1	n.275-1839T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2902+6934A>G		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.425+35817T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0338 Hom.: 190

Bravo AF: 0.0835

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.24

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: rs12762512; hg19: chr10-78697597;