Genetic Variant FDFT1:c.100-51_100-46dupCACTCC (chr8-11808709-G-GTCCCAC) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001287750.2(FDFT1):c.226_231dupCACTCC(p.His76_Ser77dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00090 ( 8 hom. )

Consequence

FDFT1
NM_001287750.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.258

Publications

15 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: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001287750.2

BS2

High Homozygotes in GnomAdExome4 at 8 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.100-51_100-46dupCACTCC		intron	N/A	NP_004453.3
FDFT1	NM_001287750.2		c.226_231dupCACTCC	p.His76_Ser77dup	conservative_inframe_insertion	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
FDFT1	NM_001287742.2		c.100-51_100-46dupCACTCC		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.100-51_100-46dupCACTCC		intron	N/A	ENSP00000220584.4	P37268-1
FDFT1	ENST00000529464.5	TSL:1	n.100-924_100-919dupCACTCC		intron	N/A	ENSP00000434770.1	E9PNJ2
FDFT1	ENST00000525954.5	TSL:2	c.226_231dupCACTCC	p.His76_Ser77dup	conservative_inframe_insertion	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

157

AN:

148920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00133

Gnomad ASJ

AF:

0.000868

Gnomad EAS

AF:

0.00121

Gnomad SAS

AF:

0.000859

Gnomad FIN

AF:

0.000971

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.000802

Gnomad OTH

AF:

0.00147

GnomAD4 exome

AF:

0.000901

AC:

1231

AN:

1366036

Hom.:

Cov.:

AF XY:

0.000905

AC XY:

609

AN XY:

672636

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

31490

American (AMR)

AF:

0.00450

AC:

158

AN:

35134

Ashkenazi Jewish (ASJ)

AF:

0.000298

AC:

AN:

23468

East Asian (EAS)

AF:

0.00513

AC:

184

AN:

35834

South Asian (SAS)

AF:

0.000658

AC:

AN:

75938

European-Finnish (FIN)

AF:

0.00128

AC:

AN:

39866

Middle Eastern (MID)

AF:

0.00180

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.000605

AC:

642

AN:

1061688

Other (OTH)

AF:

0.00138

AC:

AN:

57050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00106

AC:

158

AN:

149032

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

72636

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

40010

American (AMR)

AF:

0.00139

AC:

AN:

15080

Ashkenazi Jewish (ASJ)

AF:

0.000868

AC:

AN:

3456

East Asian (EAS)

AF:

0.00121

AC:

AN:

4952

South Asian (SAS)

AF:

0.000859

AC:

AN:

4654

European-Finnish (FIN)

AF:

0.000971

AC:

AN:

10296

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000802

AC:

AN:

67320

Other (OTH)

AF:

0.00145

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

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:

0.00290

Hom.:

2006

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over