10-77592981-T-C

Variant names:

• chr10-77592981-T-C
• rs2253545
• NM_001161352.2:c.378+44284A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.378+44284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,220 control chromosomes in the GnomAD database, including 63,811 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 0.91 (63811 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.378+44284A>G		intron_variant	Intron 1 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.378+44284A>G		intron_variant	Intron 1 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139112 AN: 152102 Hom.: 63763 Cov.: 32

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.915 AC: 139219 AN: 152220 Hom.: 63811 Cov.: 32 AF XY: 0.910 AC XY: 67738 AN XY: 74426

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.944

Gnomad4 OTH AF: 0.933

Alfa AF: 0.924 Hom.: 10960

Bravo AF: 0.916

Asia WGS AF: 0.951 AC: 3308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.81

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: rs2253545; hg19: chr10-79352739;