chr10-77483744-G-T

Position:

• chr10-77483744-G-T

Variant summary

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

The ENST00000286628.14(KCNMA1):​c.379-79721C>A variant causes a intron change. The variant allele was found at a frequency of 0.545 in 152,006 control chromosomes in the GnomAD database, including 22,791 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 0.54 (22791 hom., cov: 32)
• Consequence: KCNMA1 ENST00000286628.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.379-79721C>A		intron_variant		ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.379-79721C>A		intron_variant		1	NM_001161352.2	ENSP00000286628	A2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82779 AN: 151888 Hom.: 22786 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.545 AC: 82817 AN: 152006 Hom.: 22791 Cov.: 32 AF XY: 0.551 AC XY: 40913 AN XY: 74292

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.557

Alfa AF: 0.531 Hom.: 12686

Bravo AF: 0.545

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.47

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: rs35791; hg19: chr10-79243502;