rs2673402

Positions:

• chr10-77597949-T-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+39316A>T 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 152,248 control chromosomes in the GnomAD database, including 63,956 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 0.92 (63956 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• 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/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.378+39316A>T		intron_variant		ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.378+39316A>T		intron_variant		1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139275 AN: 152130 Hom.: 63908 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.943

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: 139382 AN: 152248 Hom.: 63956 Cov.: 32 AF XY: 0.910 AC XY: 67749 AN XY: 74434

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.933

Alfa AF: 0.930 Hom.: 8167

Bravo AF: 0.918

Asia WGS AF: 0.954 AC: 3318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.72

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: rs2673402; hg19: chr10-79357707;