NM_004462.5:c.511-1695T>C

Variant names:

• chr8-11824329-T-C
• rs17149412
• NM_004462.5:c.511-1695T>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.511-1695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,052 control chromosomes in the GnomAD database, including 5,900 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 0.25 (5900 hom., cov: 33)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.511-1695T>C		intron_variant	Intron 4 of 7	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.511-1695T>C		intron_variant	Intron 4 of 7	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37611 AN: 151934 Hom.: 5904 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.247 AC: 37621 AN: 152052 Hom.: 5900 Cov.: 33 AF XY: 0.259 AC XY: 19280 AN XY: 74310

African (AFR) AF: 0.133 AC: 5536 AN: 41496

American (AMR) AF: 0.290 AC: 4430 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.776 AC: 3996 AN: 5150

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4830

European-Finnish (FIN) AF: 0.371 AC: 3911 AN: 10534

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16751 AN: 67972

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.226 Hom.: 530

Bravo AF: 0.241

Asia WGS AF: 0.483 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.53
PhyloP100		-0.80
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: rs17149412; hg19: chr8-11681838;