1-155309931-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002004.4(FDPS):c.142C>T(p.Arg48Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,604,308 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0066 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 15 hom. )

Consequence

FDPS
NM_002004.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.32

Variant links:

Genes affected

FDPS (HGNC:3631): (farnesyl diphosphate synthase) This gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

FDPS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005872637).

BP6

Variant 1-155309931-C-T is Benign according to our data. Variant chr1-155309931-C-T is described in ClinVar as [Benign]. Clinvar id is 3042548.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00665 (1012/152252) while in subpopulation AFR AF= 0.019 (791/41540). AF 95% confidence interval is 0.0179. There are 6 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1012 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDPS	NM_002004.4 link	c.142C>T	p.Arg48Cys	missense_variant	Exon 2 of 11	ENST00000368356.9	NP_001995.1	P14324-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDPS	ENST00000368356.9 link	c.142C>T	p.Arg48Cys	missense_variant	Exon 2 of 11	2	NM_002004.4	ENSP00000357340.4		P14324-1

Frequencies

GnomAD3 genomes

AF:

0.00665

AC:

1011

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00291

AC:

705

AN:

242260

Hom.:

AF XY:

0.00244

AC XY:

321

AN XY:

131536

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.000718

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000267

Gnomad FIN exome

AF:

0.00161

Gnomad NFE exome

AF:

0.00222

Gnomad OTH exome

AF:

0.00288

GnomAD4 exome

AF:

0.00226

AC:

3279

AN:

1452056

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1545

AN XY:

720624

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.000694

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.000980

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00665

AC:

1012

AN:

152252

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

485

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00334

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00720

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.0202

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00323

AC:

392

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FDPS-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.89

.;D;D;D

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.31

N;.;N;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;.;D;.

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.68

MVP

0.59

MPC

1.2

ClinPred

0.037

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.23

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

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