Genetic Variant MVD:c.678+52G>A (chr16-88655604-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002461.3(MVD):c.678+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,540,272 control chromosomes in the GnomAD database, including 16,236 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 0.12 ( 1152 hom., cov: 34)

Exomes 𝑓: 0.14 ( 15084 hom. )

Consequence

MVD
NM_002461.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

13 publications found

Variant links:

Genes affected

MVD (HGNC:7529): (mevalonate diphosphate decarboxylase) The enzyme mevalonate pyrophosphate decarboxylase catalyzes the conversion of mevalonate pyrophosphate into isopentenyl pyrophosphate in one of the early steps in cholesterol biosynthesis. It decarboxylates and dehydrates its substrate while hydrolyzing ATP. [provided by RefSeq, Jul 2008]

MVD Gene-Disease associations (from GenCC):

porokeratosis 7, multiple types
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
disseminated superficial actinic porokeratosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MVD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002461.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVD	NM_002461.3	MANE Select	c.678+52G>A		intron	N/A	NP_002452.1	P53602

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MVD	ENST00000301012.8	TSL:1 MANE Select	c.678+52G>A	intron	N/A	ENSP00000301012.3	P53602
MVD	ENST00000565149.5	TSL:1	n.1237+52G>A	intron	N/A
MVD	ENST00000899622.1		c.798+52G>A	intron	N/A	ENSP00000569681.1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17577

AN:

152112

Hom.:

1153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0979

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0802

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.0788

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.141

AC:

195936

AN:

1388044

Hom.:

15084

Cov.:

AF XY:

0.145

AC XY:

99253

AN XY:

684820

show subpopulations

African (AFR)

AF:

0.0547

AC:

1720

AN:

31424

American (AMR)

AF:

0.0785

AC:

2792

AN:

35566

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

5222

AN:

25006

East Asian (EAS)

AF:

0.0541

AC:

1933

AN:

35700

South Asian (SAS)

AF:

0.229

AC:

18112

AN:

78986

European-Finnish (FIN)

AF:

0.0838

AC:

3709

AN:

44282

Middle Eastern (MID)

AF:

0.222

AC:

914

AN:

4120

European-Non Finnish (NFE)

AF:

0.143

AC:

153264

AN:

1075340

Other (OTH)

AF:

0.144

AC:

8270

AN:

57620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9718

19436

29155

38873

48591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5502

11004

16506

22008

27510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.115

AC:

17577

AN:

152228

Hom.:

1152

Cov.:

AF XY:

0.114

AC XY:

8489

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0595

AC:

2469

AN:

41530

American (AMR)

AF:

0.0977

AC:

1495

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

766

AN:

3472

East Asian (EAS)

AF:

0.0798

AC:

413

AN:

5176

South Asian (SAS)

AF:

0.231

AC:

1115

AN:

4834

European-Finnish (FIN)

AF:

0.0788

AC:

837

AN:

10618

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

10024

AN:

67984

Other (OTH)

AF:

0.136

AC:

286

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

824

1648

2471

3295

4119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

2021

Bravo

AF:

0.111

Asia WGS

AF:

0.140

AC:

489

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.018

(source)

DANN

Benign

0.68

PhyloP100

-1.7

RBP_binding_hub_radar

0.77

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over