chr10-76885695-G-A

Variant names:

• chr10-76885695-G-A
• rs10762733
• NM_001161352.2:c.*1571C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161352.2(KCNMA1):​c.*1571C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 984,658 control chromosomes in the GnomAD database, including 151,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19488 hom., cov: 31)
  • Exomes 𝑓: 0.56 (132450 hom.)
• Consequence: KCNMA1 NM_001161352.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.252

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-76885695-G-A is Benign according to our data. Variant chr10-76885695-G-A is described in ClinVar as [Benign]. Clinvar id is 300933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.*1571C>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628	c.*1571C>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75009 AN: 151776 Hom.: 19479 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.562 AC: 467923 AN: 832764 Hom.: 132450 Cov.: 32 AF XY: 0.562 AC XY: 216310 AN XY: 384588

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.494 AC: 75032 AN: 151894 Hom.: 19488 Cov.: 31 AF XY: 0.487 AC XY: 36163 AN XY: 74218

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.516

Alfa AF: 0.556 Hom.: 23183

Bravo AF: 0.477

Asia WGS AF: 0.314 AC: 1092 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Generalized epilepsy-paroxysmal dyskinesia syndrome Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.69

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: rs10762733; hg19: chr10-78645453;