rs10762732

chr10-76870739-T-Cchr10-76870739-T-G

Variant summary

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

The ENST00000604624.6(KCNMA1):c.*7130A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,374 control chromosomes in the GnomAD database, including 27,778 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 0.60 (27707 hom., cov: 32)
  • Exomes 𝑓: 0.64 (71 hom.)
• Consequence: KCNMA1 ENST00000604624.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001014797.3	c.*7130A>G		3_prime_UTR_variant	29/29
KCNMA1	NM_001271518.2	c.*7130A>G		3_prime_UTR_variant	28/28
KCNMA1	NM_001322829.2	c.*7130A>G		3_prime_UTR_variant	29/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000604624.6	c.*7130A>G		3_prime_UTR_variant	28/28	1
KCNMA1	ENST00000638991.1	c.*7130A>G		3_prime_UTR_variant	29/29	5		A2
KCNMA1	ENST00000639601.1	c.*7130A>G		3_prime_UTR_variant	28/28	5		A2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90508 AN: 151884 Hom.: 27669 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.642 AC: 239 AN: 372 Hom.: 71 Cov.: 0 AF XY: 0.633 AC XY: 181 AN XY: 286

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.596 AC: 90594 AN: 152002 Hom.: 27707 Cov.: 32 AF XY: 0.598 AC XY: 44453 AN XY: 74296

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.541

Alfa AF: 0.535 Hom.: 22287

Bravo AF: 0.597

Asia WGS AF: 0.515 AC: 1789 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	0.33
Dann	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10762732; hg19: chr10-78630497;