Genetic Variant FDFT1:c.100-232G>C (chr8-11808562-G-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001287750.2(FDFT1):c.45G>C(p.Lys15Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00761 in 1,366,542 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 50 hom. )

Consequence

FDFT1
NM_001287750.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 5.26

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

FDFT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013361603).

BP6

Variant 8-11808562-G-C is Benign according to our data. Variant chr8-11808562-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1049617.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287750.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FDFT1	NM_004462.5	MANE Select	c.100-232G>C		intron	N/A	NP_004453.3
FDFT1	NM_001287750.2		c.45G>C	p.Lys15Asn	missense	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
FDFT1	NM_001287742.2		c.100-232G>C		intron	N/A	NP_001274671.1	Q6IAX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.100-232G>C		intron	N/A	ENSP00000220584.4	P37268-1
FDFT1	ENST00000529464.5	TSL:1	n.100-1105G>C		intron	N/A	ENSP00000434770.1	E9PNJ2
FDFT1	ENST00000525954.5	TSL:2	c.45G>C	p.Lys15Asn	missense	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

693

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00383

GnomAD4 exome

AF:

0.00799

AC:

9707

AN:

1214276

Hom.:

Cov.:

AF XY:

0.00778

AC XY:

4558

AN XY:

586070

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

23610

American (AMR)

AF:

0.00255

AC:

AN:

12530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16524

East Asian (EAS)

AF:

0.00

AC:

AN:

28976

South Asian (SAS)

AF:

0.000415

AC:

AN:

52962

European-Finnish (FIN)

AF:

0.00155

AC:

AN:

28946

Middle Eastern (MID)

AF:

0.000287

AC:

AN:

3482

European-Non Finnish (NFE)

AF:

0.00925

AC:

9220

AN:

997248

Other (OTH)

AF:

0.00698

AC:

349

AN:

49998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

584

1169

1753

2338

2922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.00454

AC:

692

AN:

152266

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41560

American (AMR)

AF:

0.00425

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00815

AC:

554

AN:

68010

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000641

Hom.:

Bravo

AF:

0.00483

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00701

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

FDFT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.91

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.43

MetaRNN

Benign

0.013

PhyloP100

5.3

GERP RS

3.5

PromoterAI

0.14

Neutral

(source)

gMVP

0.26

Mutation Taster

=95/5

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over