Variant rs2270374 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_000431.4(MVK):c.885+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,601,586 control chromosomes in the GnomAD database, including 22,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1484 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21297 hom. )

Consequence

MVK
NM_000431.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.45

Variant links:

Genes affected

MVK (HGNC:7530): (mevalonate kinase) This gene encodes the peroxisomal enzyme mevalonate kinase. Mevalonate is a key intermediate, and mevalonate kinase a key early enzyme, in isoprenoid and sterol synthesis. Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. Defects in this gene also cause hyperimmunoglobulinaemia D and periodic fever syndrome, a disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MVK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-109591381-G-A is Benign according to our data. Variant chr12-109591381-G-A is described in ClinVar as [Benign]. Clinvar id is 439923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-109591381-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVK	NM_000431.4 linkuse as main transcript	c.885+24G>A		intron_variant		ENST00000228510.8	NP_000422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVK	ENST00000228510.8 linkuse as main transcript	c.885+24G>A		intron_variant		1	NM_000431.4	ENSP00000228510	P1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19106

AN:

152194

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.149

AC:

37314

AN:

249608

Hom.:

2941

AF XY:

0.152

AC XY:

20580

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.0342

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.168

AC:

243852

AN:

1449274

Hom.:

21297

Cov.:

AF XY:

0.167

AC XY:

120763

AN XY:

721800

show subpopulations

Gnomad4 AFR exome

AF:

0.0309

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.125

AC:

19104

AN:

152312

Hom.:

1484

Cov.:

AF XY:

0.122

AC XY:

9052

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.157

Hom.:

457

Bravo

AF:

0.127

Asia WGS

AF:

0.143

AC:

498

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 07, 2018	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0010

DANN

Benign

0.45

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