ENST00000565149.5:n.2342G>A

Variant names:

• chr16-88651945-C-T
• rs9932581
• ENST00000565149.5:n.2342G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000565149.5(MVD):​n.2342G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 163,318 control chromosomes in the GnomAD database, including 13,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12087 hom., cov: 34)
  • Exomes 𝑓: 0.41 (1065 hom.)
• Consequence: MVD ENST00000565149.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.43
• Publications: 41 publications found

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, Labcorp Genetics (formerly Invitae), G2P
• disseminated superficial actinic porokeratosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-88651945-C-T is Benign according to our data. Variant chr16-88651945-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000565149.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVD	NM_002461.3	MANE Select	c.*580G>A		3_prime_UTR	Exon 10 of 10	NP_002452.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVD	ENST00000565149.5	TSL:1	n.2342G>A		non_coding_transcript_exon	Exon 6 of 6
	MVD	ENST00000301012.8	TSL:1 MANE Select	c.*580G>A		3_prime_UTR	Exon 10 of 10	ENSP00000301012.3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59407 AN: 151974 Hom.: 12084 Cov.: 34

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.407 AC: 4568 AN: 11226 Hom.: 1065 Cov.: 0 AF XY: 0.406 AC XY: 2564 AN XY: 6318

African (AFR) AF: 0.313 AC: 15 AN: 48

American (AMR) AF: 0.527 AC: 965 AN: 1832

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 53 AN: 152

East Asian (EAS) AF: 0.583 AC: 35 AN: 60

South Asian (SAS) AF: 0.407 AC: 1077 AN: 2648

European-Finnish (FIN) AF: 0.347 AC: 86 AN: 248

Middle Eastern (MID) AF: 0.361 AC: 13 AN: 36

European-Non Finnish (NFE) AF: 0.376 AC: 2140 AN: 5696

Other (OTH) AF: 0.364 AC: 184 AN: 506

GnomAD4 genome AF: 0.391 AC: 59424 AN: 152092 Hom.: 12087 Cov.: 34 AF XY: 0.394 AC XY: 29308 AN XY: 74356

African (AFR) AF: 0.283 AC: 11737 AN: 41506

American (AMR) AF: 0.481 AC: 7364 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1498 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3035 AN: 5162

South Asian (SAS) AF: 0.436 AC: 2103 AN: 4828

European-Finnish (FIN) AF: 0.427 AC: 4526 AN: 10590

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27624 AN: 67926

Other (OTH) AF: 0.425 AC: 894 AN: 2106

Alfa AF: 0.396 Hom.: 13625

Bravo AF: 0.392

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.81
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9932581; hg19: chr16-88718353;