Variant rs1131824 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001161352.2(KCNMA1):c.687C>T(p.Phe229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,600,698 control chromosomes in the GnomAD database, including 108,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15184 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93170 hom. )

Consequence

KCNMA1
NM_001161352.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 10-77184832-G-A is Benign according to our data. Variant chr10-77184832-G-A is described in ClinVar as [Benign]. Clinvar id is 129328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-77184832-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 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.687C>T	p.Phe229=	synonymous_variant	4/28	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14 linkuse as main transcript	c.687C>T	p.Phe229=	synonymous_variant	4/28	1	NM_001161352.2	ENSP00000286628	A2	Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64599

AN:

151846

Hom.:

15161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.383

GnomAD3 exomes

AF:

0.348

AC:

87164

AN:

250790

Hom.:

16512

AF XY:

0.346

AC XY:

46955

AN XY:

135522

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.267

Gnomad SAS exome

AF:

0.325

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.352

AC:

510383

AN:

1448734

Hom.:

93170

Cov.:

AF XY:

0.351

AC XY:

253401

AN XY:

721448

show subpopulations

Gnomad4 AFR exome

AF:

0.636

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.371

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.425

AC:

64660

AN:

151964

Hom.:

15184

Cov.:

AF XY:

0.423

AC XY:

31414

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.386

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.369

Hom.:

19140

Bravo

AF:

0.428

Asia WGS

AF:

0.313

AC:

1086

AN:

3478

EpiCase

AF:

0.355

EpiControl

AF:

0.359

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Generalized epilepsy-paroxysmal dyskinesia syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 28, 2014	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Cerebellar atrophy, developmental delay, and seizures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Liang-Wang syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.77

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