rs1873695

Positions:

• chr10-76934455-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.2902+10318G>A		intron_variant		ENST00000286628.14	NP_001154824.1
KCNMA1-AS1	NR_120655.1	n.457+32433C>T		intron_variant, non_coding_transcript_variant
LOC124902466	XR_007062207.1	n.274+4218C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2902+10318G>A		intron_variant		1	NM_001161352.2	ENSP00000286628	A2
KCNMA1-AS1	ENST00000458661.6	n.425+32433C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.106

Alfa AF: 0.137 Hom.: 1137

Bravo AF: 0.154

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.64

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: rs1873695; hg19: chr10-78694213;