8-11802542-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000533405.2(ENSG00000255046):​n.27T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 568,040 control chromosomes in the GnomAD database, including 158,526 homozygotes. 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: 𝑓 0.74 (42134 hom., cov: 35)
  • Exomes 𝑓: 0.75 (116392 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.-291A>G		upstream_gene_variant		ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.-291A>G		upstream_gene_variant		1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113096 AN: 152120 Hom.: 42080 Cov.: 35

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.730

GnomAD4 exome AF: 0.747 AC: 310514 AN: 415802 Hom.: 116392 Cov.: 0 AF XY: 0.747 AC XY: 171025 AN XY: 229082

African (AFR) AF: 0.731 AC: 9005 AN: 12316

American (AMR) AF: 0.782 AC: 23783 AN: 30414

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 10215 AN: 15370

East Asian (EAS) AF: 0.714 AC: 14135 AN: 19802

South Asian (SAS) AF: 0.783 AC: 47511 AN: 60664

European-Finnish (FIN) AF: 0.741 AC: 15483 AN: 20904

Middle Eastern (MID) AF: 0.650 AC: 2198 AN: 3382

European-Non Finnish (NFE) AF: 0.744 AC: 171753 AN: 230730

Other (OTH) AF: 0.739 AC: 16431 AN: 22220

GnomAD4 genome AF: 0.744 AC: 113208 AN: 152238 Hom.: 42134 Cov.: 35 AF XY: 0.743 AC XY: 55327 AN XY: 74422

African (AFR) AF: 0.727 AC: 30224 AN: 41546

American (AMR) AF: 0.775 AC: 11853 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3596 AN: 5172

South Asian (SAS) AF: 0.792 AC: 3824 AN: 4830

European-Finnish (FIN) AF: 0.750 AC: 7952 AN: 10600

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51018 AN: 67996

Other (OTH) AF: 0.733 AC: 1550 AN: 2114

Alfa AF: 0.742 Hom.: 15310

Bravo AF: 0.743

Asia WGS AF: 0.775 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.1
DANN	Benign	0.63
PhyloP100		0.52
PromoterAI		0.0060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV55041875; COSMIC: COSV55041875;