rs1907737

Positions:

• chr10-76956404-C-T

Variant summary

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

The NM_001161352.2(KCNMA1):​c.2361-2480G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,796 control chromosomes in the GnomAD database, including 19,641 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 0.50 (19641 hom., cov: 30)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.2361-2480G>A		intron_variant		ENST00000286628.14	NP_001154824.1
KCNMA1-AS1	NR_120655.1	n.458-21206C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2361-2480G>A		intron_variant		1	NM_001161352.2	ENSP00000286628	A2
KCNMA1-AS1	ENST00000458661.6	n.426-21206C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75528 AN: 151676 Hom.: 19632 Cov.: 30

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.498 AC: 75561 AN: 151796 Hom.: 19641 Cov.: 30 AF XY: 0.500 AC XY: 37082 AN XY: 74168

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.485

Alfa AF: 0.535 Hom.: 4525

Bravo AF: 0.476

Asia WGS AF: 0.616 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.035
DANN	Benign	0.27

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: rs1907737; hg19: chr10-78716162;