8-11802542-A-C

Variant names:

• chr8-11802542-A-C
• rs2645429
• ENST00000533405.2:n.27T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000533405.2(ENSG00000255046):​n.27T>G variant causes a non coding transcript exon 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)
• Consequence: ENSG00000255046 ENST00000533405.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 18 publications found

Genes affected

ENSG00000255046 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533405.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000255046	ENST00000533405.2	TSL:3	n.27T>G		non_coding_transcript_exon	Exon 1 of 2
	FDFT1	ENST00000530337.6	TSL:3	c.-75+87A>C		intron	N/A	ENSP00000431852.2
	FDFT1	ENST00000615631.5	TSL:5	c.-74-217A>C		intron	N/A	ENSP00000481481.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.8
DANN	Benign	0.59
PhyloP100		0.52
PromoterAI		0.039	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;