Variant 10-76885309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001161352.2(KCNMA1):c.*1957C>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 0.786 in 865,032 control chromosomes in the GnomAD database, including 268,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48763 hom., cov: 28)

Exomes 𝑓: 0.78 ( 220093 hom. )

Consequence

KCNMA1
NM_001161352.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.449

Variant links:

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 links:

KCNMA1 (HGNC:):

KCNMA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-76885309-G-A is Benign according to our data. Variant chr10-76885309-G-A is described in ClinVar as [Benign]. Clinvar id is 300927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMA1	NM_001161352.2 linkuse as main transcript	c.*1957C>T		3_prime_UTR_variant	28/28	ENST00000286628.14	NP_001154824.1	Q12791-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628 linkuse as main transcript	c.*1957C>T		3_prime_UTR_variant	28/28	1	NM_001161352.2	ENSP00000286628.8		Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

119662

AN:

148894

Hom.:

48735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.905

Gnomad AMI

AF:

0.810

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.867

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.795

Gnomad OTH

AF:

0.766

GnomAD4 exome

AF:

0.782

AC:

560354

AN:

716114

Hom.:

220093

Cov.:

AF XY:

0.783

AC XY:

261077

AN XY:

333562

show subpopulations

Gnomad4 AFR exome

AF:

0.914

Gnomad4 AMR exome

AF:

0.651

Gnomad4 ASJ exome

AF:

0.758

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.891

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.757

GnomAD4 genome

AF:

0.804

AC:

119707

AN:

148918

Hom.:

48763

Cov.:

AF XY:

0.800

AC XY:

58051

AN XY:

72598

show subpopulations

Gnomad4 AFR

AF:

0.905

Gnomad4 AMR

AF:

0.706

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.499

Gnomad4 SAS

AF:

0.613

Gnomad4 FIN

AF:

0.867

Gnomad4 NFE

AF:

0.795

Gnomad4 OTH

AF:

0.767

Alfa

AF:

0.788

Hom.:

24662

Bravo

AF:

0.795

Asia WGS

AF:

0.618

AC:

2142

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Generalized epilepsy-paroxysmal dyskinesia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.4

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over