rs816827

Positions:

• chr10-77531591-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.378+105674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 152,254 control chromosomes in the GnomAD database, including 699 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 0.086 (699 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

LOC124902464 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.378+105674C>T		intron_variant		ENST00000286628.14	NP_001154824.1
LOC124902464	XR_007062205.1	n.6219C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.378+105674C>T		intron_variant		1	NM_001161352.2	ENSP00000286628	A2

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13031 AN: 152136 Hom.: 699 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0857 AC: 13041 AN: 152254 Hom.: 699 Cov.: 33 AF XY: 0.0905 AC XY: 6737 AN XY: 74432

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0710 Hom.: 39

Bravo AF: 0.0826

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.9
DANN	Benign	0.76

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: rs816827; hg19: chr10-79291349;