8-11808296-C-T

Position:

• chr8-11808296-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004462.5(FDFT1):​c.100-498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,223,746 control chromosomes in the GnomAD database, including 259,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.58 (26997 hom., cov: 31)
  • Exomes 𝑓: 0.66 (232940 hom.)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-11808296-C-T is Benign according to our data. Variant chr8-11808296-C-T is described in ClinVar as [Benign]. Clinvar id is 3054358.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.100-498C>T		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.100-498C>T		intron_variant		1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88199 AN: 151760 Hom.: 26964 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.657 AC: 704153 AN: 1071868 Hom.: 232940 Cov.: 39 AF XY: 0.656 AC XY: 331916 AN XY: 506062

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.581 AC: 88277 AN: 151878 Hom.: 26997 Cov.: 31 AF XY: 0.587 AC XY: 43538 AN XY: 74232

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.594

Alfa AF: 0.606 Hom.: 3626

Bravo AF: 0.570

Asia WGS AF: 0.701 AC: 2441 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FDFT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2020

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	-0.77
CADD	Benign	2.1
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1736070; hg19: chr8-11665805;