8-11802542-A-T

Variant names:

• chr8-11802542-A-T
• rs2645429
• NM_001287742.2:c.-75+87A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001287742.2(FDFT1):​c.-75+87A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FDFT1 NM_001287742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 18 publications found

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

ENSG00000255046 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287742.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	NM_001287742.2		c.-75+87A>T		intron	N/A	NP_001274671.1
	FDFT1	NM_001287743.2		c.-74-217A>T		intron	N/A	NP_001274672.1
	FDFT1	NM_001287744.2		c.-93-6252A>T		intron	N/A	NP_001274673.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000530337.6	TSL:3	c.-75+87A>T		intron	N/A	ENSP00000431852.2
	FDFT1	ENST00000615631.5	TSL:5	c.-74-217A>T		intron	N/A	ENSP00000481481.1
	FDFT1	ENST00000866105.1		c.-75+87A>T		intron	N/A	ENSP00000536164.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 416248 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 229320

African (AFR) AF: 0.00 AC: 0 AN: 12328

American (AMR) AF: 0.00 AC: 0 AN: 30432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15398

East Asian (EAS) AF: 0.00 AC: 0 AN: 19838

South Asian (SAS) AF: 0.00 AC: 0 AN: 60678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 231026

Other (OTH) AF: 0.00 AC: 0 AN: 22238

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 15310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		0.52
PromoterAI		0.011	Neutral

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

Other links and lift over

dbSNP: rs2645429; hg19: chr8-11660051;