10-77147696-T-A

Variant names:

• chr10-77147696-T-A
• rs2616652
• NM_001161352.2:c.809-26648A>T

Variant summary

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

The NM_001161352.2(KCNMA1):​c.809-26648A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,210 control chromosomes in the GnomAD database, including 57,614 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 0.87 (57588 hom., cov: 31)
  • Exomes 𝑓: 0.81 (26 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 1 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-AS2 (HGNC:51214): (KCNMA1 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.809-26648A>T		intron_variant	Intron 5 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.809-26648A>T		intron_variant	Intron 5 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132256 AN: 152018 Hom.: 57543 Cov.: 31

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.871

GnomAD4 exome AF: 0.811 AC: 60 AN: 74 Hom.: 26 Cov.: 0 AF XY: 0.794 AC XY: 54 AN XY: 68

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.833 AC: 5 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.803 AC: 53 AN: 66

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.870 AC: 132357 AN: 152136 Hom.: 57588 Cov.: 31 AF XY: 0.871 AC XY: 64764 AN XY: 74378

African (AFR) AF: 0.899 AC: 37344 AN: 41518

American (AMR) AF: 0.915 AC: 13989 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3071 AN: 3472

East Asian (EAS) AF: 0.915 AC: 4711 AN: 5150

South Asian (SAS) AF: 0.864 AC: 4152 AN: 4808

European-Finnish (FIN) AF: 0.838 AC: 8868 AN: 10578

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57412 AN: 67996

Other (OTH) AF: 0.873 AC: 1846 AN: 2114

Alfa AF: 0.852 Hom.: 6446

Bravo AF: 0.878

Asia WGS AF: 0.879 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		2.7
Mutation Taster		=99/1	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: rs2616652; hg19: chr10-78907454;