8-11804057-G-C

Variant names:

• chr8-11804057-G-C
• rs9650662
• NM_004462.5:c.99+1126G>C

Variant summary

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

The NM_004462.5(FDFT1):​c.99+1126G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,218 control chromosomes in the GnomAD database, including 2,406 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 0.16 (2406 hom., cov: 33)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004462.5. 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_004462.5	MANE Select	c.99+1126G>C		intron	N/A	NP_004453.3
	FDFT1	NM_001287742.2		c.99+1126G>C		intron	N/A	NP_001274671.1	Q6IAX1
	FDFT1	NM_001287743.2		c.99+1126G>C		intron	N/A	NP_001274672.1	P37268-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.99+1126G>C		intron	N/A	ENSP00000220584.4	P37268-1
	FDFT1	ENST00000529464.5	TSL:1	n.99+1126G>C		intron	N/A	ENSP00000434770.1	E9PNJ2
	FDFT1	ENST00000938356.1		c.99+1126G>C		intron	N/A	ENSP00000608415.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24029 AN: 152100 Hom.: 2406 Cov.: 33

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24039 AN: 152218 Hom.: 2406 Cov.: 33 AF XY: 0.163 AC XY: 12158 AN XY: 74418

African (AFR) AF: 0.0800 AC: 3321 AN: 41536

American (AMR) AF: 0.156 AC: 2380 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2421 AN: 5180

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4832

European-Finnish (FIN) AF: 0.196 AC: 2078 AN: 10576

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11652 AN: 68014

Other (OTH) AF: 0.162 AC: 342 AN: 2112

Alfa AF: 0.0813 Hom.: 94

Bravo AF: 0.151

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.50
PhyloP100		-2.0
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: rs9650662; hg19: chr8-11661566;