rs35773

Positions:

• chr10-77373975-T-C
• chr10-77373975-T-G

Variant summary

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

The NM_001161352.2(KCNMA1):​c.540+29887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,216 control chromosomes in the GnomAD database, including 50,315 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 0.81 (50287 hom., cov: 32)
  • Exomes 𝑓: 0.82 (28 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81

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-AS3 (HGNC:51215): (KCNMA1 antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.540+29887A>G		intron_variant		ENST00000286628.14
KCNMA1-AS3	NR_126365.1	n.1049+140T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.540+29887A>G		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS3	ENST00000418515.1	n.516+140T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123337 AN: 152016 Hom.: 50234 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.815

GnomAD4 exome AF: 0.817 AC: 67 AN: 82 Hom.: 28 AF XY: 0.814 AC XY: 57 AN XY: 70

Gnomad4 AFR exome AF: 0.750

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.813

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.811 AC: 123447 AN: 152134 Hom.: 50287 Cov.: 32 AF XY: 0.804 AC XY: 59817 AN XY: 74374

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.815

Alfa AF: 0.801 Hom.: 6057

Bravo AF: 0.816

Asia WGS AF: 0.730 AC: 2537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.51

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: rs35773; hg19: chr10-79133733;