Genetic Variant NM_004462.5:c.21T>C (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

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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