rs9932581

Positions:

• chr16-88651945-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002461.3(MVD):​c.*580G>A variant causes a 3 prime UTR 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 NM_002461.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.43

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVD	NM_002461.3	c.*580G>A		3_prime_UTR_variant	10/10	ENST00000301012.8	NP_002452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVD	ENST00000301012	c.*580G>A		3_prime_UTR_variant	10/10	1	NM_002461.3	ENSP00000301012.3
MVD	ENST00000565149.5	n.2342G>A		non_coding_transcript_exon_variant	6/6	1

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

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.364

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

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.425

Alfa AF: 0.409 Hom.: 10502

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs9932581; hg19: chr16-88718353;