16-88652457-C-T

Variant names:

• chr16-88652457-C-T
• rs8854
• ENST00000565149.5:n.1830G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000565149.5(MVD):​n.1830G>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 0.0981 in 1,515,130 control chromosomes in the GnomAD database, including 7,804 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 0.096 (764 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7040 hom.)
• Consequence: MVD ENST00000565149.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVD	NM_002461.3	c.*68G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000301012.8	NP_002452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVD	ENST00000565149.5	n.1830G>A		non_coding_transcript_exon_variant	Exon 6 of 6	1
MVD	ENST00000301012.8	c.*68G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_002461.3	ENSP00000301012.3
MVD	ENST00000562981.1	n.434G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
MVD	ENST00000561895.1	n.*53G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14551 AN: 152124 Hom.: 758 Cov.: 33

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.0984 AC: 134060 AN: 1362888 Hom.: 7040 Cov.: 25 AF XY: 0.0973 AC XY: 65640 AN XY: 674368

African (AFR) AF: 0.0970 AC: 2993 AN: 30848

American (AMR) AF: 0.126 AC: 4492 AN: 35650

Ashkenazi Jewish (ASJ) AF: 0.0396 AC: 988 AN: 24966

East Asian (EAS) AF: 0.00534 AC: 190 AN: 35572

South Asian (SAS) AF: 0.101 AC: 7914 AN: 78476

European-Finnish (FIN) AF: 0.113 AC: 5394 AN: 47652

Middle Eastern (MID) AF: 0.0569 AC: 279 AN: 4904

European-Non Finnish (NFE) AF: 0.102 AC: 106523 AN: 1048030

Other (OTH) AF: 0.0931 AC: 5287 AN: 56790

GnomAD4 genome AF: 0.0958 AC: 14582 AN: 152242 Hom.: 764 Cov.: 33 AF XY: 0.0968 AC XY: 7203 AN XY: 74448

African (AFR) AF: 0.0995 AC: 4135 AN: 41550

American (AMR) AF: 0.116 AC: 1776 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5178

South Asian (SAS) AF: 0.0925 AC: 447 AN: 4830

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0965 AC: 6563 AN: 67986

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0942 Hom.: 1284

Bravo AF: 0.0967

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.69
PhyloP100		-1.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
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: rs8854; hg19: chr16-88718865;