rs3736112

Positions:

• chr16-88655604-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVD	NM_002461.3	c.678+52G>A		intron_variant		ENST00000301012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MVD	ENST00000301012.8	c.678+52G>A		intron_variant		1	NM_002461.3	P1
MVD	ENST00000565149.5	n.1237+52G>A		intron_variant, non_coding_transcript_variant		1
MVD	ENST00000569177.5	c.780+52G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17577 AN: 152112 Hom.: 1153 Cov.: 34

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.: 31 AF XY: 0.145 AC XY: 99253 AN XY: 684820

Gnomad4 AFR exome AF: 0.0547

Gnomad4 AMR exome AF: 0.0785

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.0541

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.0838

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.115 AC: 17577 AN: 152228 Hom.: 1152 Cov.: 34 AF XY: 0.114 AC XY: 8489 AN XY: 74438

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.0977

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.136

Alfa AF: 0.148 Hom.: 1504

Bravo AF: 0.111

Asia WGS AF: 0.140 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.018
DANN	Benign	0.68
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		1.9

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

LitVar

Other links and lift over

dbSNP: rs3736112; hg19: chr16-88722012;