Genetic Variant FDFT1:c.100-86_100-85insCTCCCACTCCCACTCCCACTCCCA (chr8-11808704-C-CCCCACTCCCACTCCCACTCCCACT) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001287750.2(FDFT1):c.191_192insCTCCCACTCCCACTCCCACTCCCA(p.Pro63_Gln64insHisSerHisSerHisSerHisSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,323,470 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

FDFT1
NM_001287750.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.143

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001287750.2

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.100-86_100-85insCTCCCACTCCCACTCCCACTCCCA		intron	N/A	NP_004453.3
FDFT1	NM_001287750.2		c.191_192insCTCCCACTCCCACTCCCACTCCCA	p.Pro63_Gln64insHisSerHisSerHisSerHisSer	disruptive_inframe_insertion	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
FDFT1	NM_001287742.2		c.100-86_100-85insCTCCCACTCCCACTCCCACTCCCA		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.100-86_100-85insCTCCCACTCCCACTCCCACTCCCA		intron	N/A	ENSP00000220584.4	P37268-1
FDFT1	ENST00000529464.5	TSL:1	n.100-959_100-958insCTCCCACTCCCACTCCCACTCCCA		intron	N/A	ENSP00000434770.1	E9PNJ2
FDFT1	ENST00000525954.5	TSL:2	c.191_192insCTCCCACTCCCACTCCCACTCCCA	p.Pro63_Gln64insHisSerHisSerHisSerHisSer	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1323470

Hom.:

Cov.:

AF XY:

0.00000307

AC XY:

AN XY:

651776

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31308

American (AMR)

AF:

0.00

AC:

AN:

29454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22142

East Asian (EAS)

AF:

0.00

AC:

AN:

35458

South Asian (SAS)

AF:

0.0000270

AC:

AN:

73994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5004

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1030612

Other (OTH)

AF:

0.00

AC:

AN:

54800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over