10-76934455-C-T

Variant names:

• chr10-76934455-C-T
• rs1873695
• NM_001161352.2:c.2902+10318G>A

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+10318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,242 control chromosomes in the GnomAD database, including 1,972 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 0.15 (1972 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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+10318G>A		intron	N/A	NP_001154824.1
	KCNMA1	NM_001437422.1		c.2860+10318G>A		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.2851+10318G>A		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+10318G>A		intron	N/A	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.2851+10318G>A		intron	N/A	ENSP00000485867.1
	KCNMA1	ENST00000639406.1	TSL:1	c.2737+10318G>A		intron	N/A	ENSP00000491732.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23525 AN: 152124 Hom.: 1969 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.155 AC: 23550 AN: 152242 Hom.: 1972 Cov.: 33 AF XY: 0.153 AC XY: 11359 AN XY: 74446

African (AFR) AF: 0.192 AC: 7991 AN: 41532

American (AMR) AF: 0.138 AC: 2111 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.0515 AC: 267 AN: 5188

South Asian (SAS) AF: 0.0505 AC: 244 AN: 4828

European-Finnish (FIN) AF: 0.187 AC: 1980 AN: 10600

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10239 AN: 68008

Other (OTH) AF: 0.106 AC: 224 AN: 2116

Alfa AF: 0.147 Hom.: 3732

Bravo AF: 0.154

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.64
PhyloP100		0.41
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: rs1873695; hg19: chr10-78694213;