rs8854

chr16-88652457-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002461.3(MVD):c.*68G>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 0.0981 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 NM_002461.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MVD	NM_002461.3	c.*68G>A		3_prime_UTR_variant	10/10	ENST00000301012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVD	ENST00000301012.8	c.*68G>A		3_prime_UTR_variant	10/10	1	NM_002461.3	P1
MVD	ENST00000565149.5	n.1830G>A		non_coding_transcript_exon_variant	6/6	1
MVD	ENST00000562981.1	n.434G>A		non_coding_transcript_exon_variant	2/2	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

Gnomad4 AFR exome AF: 0.0970

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.0396

Gnomad4 EAS exome AF: 0.00534

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0931

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

Gnomad4 AFR AF: 0.0995

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0965

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0921 Hom.: 821

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
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9

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: rs8854; hg19: chr16-88718865;