rs11549147

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004462.5(FDFT1):c.134A>G(p.Lys45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,613,782 control chromosomes in the GnomAD database, including 5,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 428 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4748 hom. )

Consequence

FDFT1
NM_004462.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.629

Publications

24 publications found

Variant links:

Genes affected

FDFT1 (HGNC:3629): (farnesyl-diphosphate farnesyltransferase 1) This gene encodes a membrane-associated enzyme located at a branch point in the mevalonate pathway. The encoded protein is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene. [provided by RefSeq, Jul 2008]

FDFT1 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: G2P
squalene synthase deficiency
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

FDFT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015518963).

BP6

Variant 8-11808828-A-G is Benign according to our data. Variant chr8-11808828-A-G is described in ClinVar as Benign. ClinVar VariationId is 1285264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5 link	c.134A>G	p.Lys45Arg	missense_variant	Exon 2 of 8	ENST00000220584.9	NP_004453.3	P37268-1Q6IAX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9 link	c.134A>G	p.Lys45Arg	missense_variant	Exon 2 of 8	1	NM_004462.5	ENSP00000220584.4		P37268-1

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9416

AN:

152134

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.0435

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.0579

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0863

Gnomad OTH

AF:

0.0622

GnomAD2 exomes

AF:

0.0668

AC:

16761

AN:

250864

AF XY:

0.0683

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0901

Gnomad NFE exome

AF:

0.0828

Gnomad OTH exome

AF:

0.0722

GnomAD4 exome

AF:

0.0772

AC:

112772

AN:

1461528

Hom.:

4748

Cov.:

AF XY:

0.0767

AC XY:

55764

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.0184

AC:

616

AN:

33470

American (AMR)

AF:

0.0325

AC:

1452

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4212

AN:

26128

East Asian (EAS)

AF:

0.0111

AC:

439

AN:

39692

South Asian (SAS)

AF:

0.0587

AC:

5054

AN:

86170

European-Finnish (FIN)

AF:

0.0888

AC:

4739

AN:

53372

Middle Eastern (MID)

AF:

0.0719

AC:

415

AN:

5768

European-Non Finnish (NFE)

AF:

0.0820

AC:

91166

AN:

1111834

Other (OTH)

AF:

0.0775

AC:

4679

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5585

11171

16756

22342

27927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3286

6572

9858

13144

16430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0618

AC:

9406

AN:

152254

Hom.:

428

Cov.:

AF XY:

0.0606

AC XY:

4509

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0185

AC:

768

AN:

41578

American (AMR)

AF:

0.0433

AC:

663

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

553

AN:

3470

East Asian (EAS)

AF:

0.0137

AC:

AN:

5176

South Asian (SAS)

AF:

0.0569

AC:

274

AN:

4814

European-Finnish (FIN)

AF:

0.0839

AC:

891

AN:

10614

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0863

AC:

5868

AN:

67986

Other (OTH)

AF:

0.0615

AC:

130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

448

895

1343

1790

2238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0768

Hom.:

1730

Bravo

AF:

0.0555

TwinsUK

AF:

0.0841

AC:

312

ALSPAC

AF:

0.0797

AC:

307

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.0890

AC:

765

ExAC

AF:

0.0661

AC:

8022

Asia WGS

AF:

0.0430

AC:

152

AN:

3478

EpiCase

AF:

0.0857

EpiControl

AF:

0.0860

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

FDFT1-related disorder

Benign:1

Sep 05, 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). -

Squalene synthase deficiency

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

T;T;T;T;.;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.86

.;.;D;.;D;T;D

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.;L;L;.;.

PhyloP100

0.63

PrimateAI

Benign

0.44

PROVEAN

Benign

0.25

.;.;N;N;N;N;.

REVEL

Benign

0.082

Sift

Benign

0.56

.;.;T;T;T;T;.

Sift4G

Benign

0.52

T;T;T;T;T;T;.

Polyphen

0.0

B;B;.;B;.;B;.

Vest4

0.065

ClinPred

0.0021

GERP RS

3.6

PromoterAI

-0.10

Neutral

(source)

Varity_R

0.13

gMVP

0.21

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over