Genetic Variant FDFT1:p.Leu7Leu (chr8-11802853-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004462.5(FDFT1):c.21T>C(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,610,252 control chromosomes in the GnomAD database, including 22,999 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 0.19 ( 3583 hom., cov: 34)

Exomes 𝑓: 0.16 ( 19416 hom. )

Consequence

FDFT1
NM_004462.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

23 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:

ENSG00000255046 (HGNC:):

ENSG00000255046 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=1.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5 link	c.21T>C	p.Leu7Leu	synonymous_variant	Exon 1 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.21T>C	p.Leu7Leu	synonymous_variant	Exon 1 of 8	1	NM_004462.5	ENSP00000220584.4		P37268-1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29606

AN:

152180

Hom.:

3579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0871

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.130

AC:

31689

AN:

243426

AF XY:

0.128

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.0841

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.0916

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.156

AC:

227142

AN:

1457954

Hom.:

19416

Cov.:

AF XY:

0.153

AC XY:

111263

AN XY:

725062

show subpopulations

African (AFR)

AF:

0.352

AC:

11715

AN:

33262

American (AMR)

AF:

0.0900

AC:

3995

AN:

44388

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

3958

AN:

26008

East Asian (EAS)

AF:

0.0115

AC:

454

AN:

39628

South Asian (SAS)

AF:

0.107

AC:

9178

AN:

85584

European-Finnish (FIN)

AF:

0.0932

AC:

4952

AN:

53146

Middle Eastern (MID)

AF:

0.174

AC:

1000

AN:

5740

European-Non Finnish (NFE)

AF:

0.164

AC:

182237

AN:

1109990

Other (OTH)

AF:

0.160

AC:

9653

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9032

18064

27096

36128

45160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6614

13228

19842

26456

33070

<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:

0.195

AC:

29641

AN:

152298

Hom.:

3583

Cov.:

AF XY:

0.185

AC XY:

13813

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.343

AC:

14267

AN:

41540

American (AMR)

AF:

0.128

AC:

1967

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

550

AN:

3470

East Asian (EAS)

AF:

0.0149

AC:

AN:

5174

South Asian (SAS)

AF:

0.102

AC:

494

AN:

4832

European-Finnish (FIN)

AF:

0.0871

AC:

925

AN:

10622

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.159

AC:

10815

AN:

68030

Other (OTH)

AF:

0.183

AC:

388

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1202

2404

3605

4807

6009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.180

Hom.:

2060

Bravo

AF:

0.203

Asia WGS

AF:

0.0770

AC:

270

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.6

(source)

DANN

Benign

0.75

PhyloP100

1.4

PromoterAI

0.0053

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over