8-11808615-C-G

Variant names:

• chr8-11808615-C-G
• rs186055179
• NM_004462.5:c.100-179C>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001287750.2(FDFT1):​c.98C>G​(p.Thr33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,390,718 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (20 hom.)
• Consequence: FDFT1 NM_001287750.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.286

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041832626).
• BP6: Variant 8-11808615-C-G is Benign according to our data. Variant chr8-11808615-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2571307.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.100-179C>G		intron_variant	Intron 1 of 7	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.100-179C>G		intron_variant	Intron 1 of 7	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152016 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00421

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.00475 AC: 5885 AN: 1238586 Hom.: 20 Cov.: 62 AF XY: 0.00482 AC XY: 2891 AN XY: 599560

Gnomad4 AFR exome AF: 0.000700

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00231

Gnomad4 FIN exome AF: 0.00205

Gnomad4 NFE exome AF: 0.00515

Gnomad4 OTH exome AF: 0.00411

GnomAD4 genome AF: 0.00274 AC: 417 AN: 152132 Hom.: 2 Cov.: 33 AF XY: 0.00241 AC XY: 179 AN XY: 74388

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.00421

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000479 Hom.: 0

Bravo AF: 0.00284

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00545 AC: 21

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FDFT1: BS2 -

FDFT1-related disorder Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.80
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0042	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs186055179; hg19: chr8-11666124;