Variant 16-88653416-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002461.3(MVD):c.1014-8T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,604,766 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 193 hom., cov: 34)

Exomes 𝑓: 0.0025 ( 154 hom. )

Consequence

MVD
NM_002461.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005020

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.139

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-88653416-A-C is Benign according to our data. Variant chr16-88653416-A-C is described in ClinVar as [Benign]. Clinvar id is 3055645.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVD	NM_002461.3 linkuse as main transcript	c.1014-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000301012.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
MVD	ENST00000301012.8 linkuse as main transcript	c.1014-8T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002461.3	P1
MVD	ENST00000565149.5 linkuse as main transcript	n.1573-8T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
MVD	ENST00000562981.1 linkuse as main transcript	n.169T>G	non_coding_transcript_exon_variant	1/2	2
MVD	ENST00000561895.1 linkuse as main transcript	n.295-8T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4217

AN:

152200

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00935

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00663

AC:

1568

AN:

236566

Hom.:

AF XY:

0.00487

AC XY:

630

AN XY:

129232

show subpopulations

Gnomad AFR exome

AF:

0.0931

Gnomad AMR exome

AF:

0.00446

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00253

AC:

3671

AN:

1452448

Hom.:

154

Cov.:

AF XY:

0.00218

AC XY:

1578

AN XY:

722678

show subpopulations

Gnomad4 AFR exome

AF:

0.0917

Gnomad4 AMR exome

AF:

0.00442

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000176

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.00555

GnomAD4 genome

AF:

0.0277

AC:

4223

AN:

152318

Hom.:

193

Cov.:

AF XY:

0.0269

AC XY:

2005

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0967

Gnomad4 AMR

AF:

0.00934

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00293

Hom.:

Bravo

AF:

0.0305

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MVD-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.2

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00050

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over