NM_004462.5:c.511-1695T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004462.5(FDFT1):​c.511-1695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,052 control chromosomes in the GnomAD database, including 5,900 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 0.25 ( 5900 hom., cov: 33)

Consequence

FDFT1
NM_004462.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.795

Publications

4 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FDFT1NM_004462.5 linkc.511-1695T>C intron_variant Intron 4 of 7 ENST00000220584.9 NP_004453.3 P37268-1Q6IAX1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FDFT1ENST00000220584.9 linkc.511-1695T>C intron_variant Intron 4 of 7 1 NM_004462.5 ENSP00000220584.4 P37268-1

Frequencies

GnomAD3 genomes
AF:
0.248
AC:
37611
AN:
151934
Hom.:
5904
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.134
Gnomad AMI
AF:
0.367
Gnomad AMR
AF:
0.290
Gnomad ASJ
AF:
0.140
Gnomad EAS
AF:
0.776
Gnomad SAS
AF:
0.330
Gnomad FIN
AF:
0.371
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.246
Gnomad OTH
AF:
0.247
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.247
AC:
37621
AN:
152052
Hom.:
5900
Cov.:
33
AF XY:
0.259
AC XY:
19280
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.133
AC:
5536
AN:
41496
American (AMR)
AF:
0.290
AC:
4430
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.140
AC:
485
AN:
3470
East Asian (EAS)
AF:
0.776
AC:
3996
AN:
5150
South Asian (SAS)
AF:
0.330
AC:
1593
AN:
4830
European-Finnish (FIN)
AF:
0.371
AC:
3911
AN:
10534
Middle Eastern (MID)
AF:
0.197
AC:
58
AN:
294
European-Non Finnish (NFE)
AF:
0.246
AC:
16751
AN:
67972
Other (OTH)
AF:
0.250
AC:
528
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1356
2713
4069
5426
6782
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
396
792
1188
1584
1980
<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:
0.226
Hom.:
530
Bravo
AF:
0.241
Asia WGS
AF:
0.483
AC:
1678
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.95
DANN
Benign
0.53
PhyloP100
-0.80
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs17149412; hg19: chr8-11681838; API