8-11802853-T-C

Variant names:

• chr8-11802853-T-C
• rs1047643
• NM_004462.5:c.21T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001287756.2(FDFT1):​c.7T>C​(p.Trp3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,610,252 control chromosomes in the GnomAD database, including 22,999 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3583 hom., cov: 34)
  • Exomes 𝑓: 0.16 (19416 hom.)
• Consequence: FDFT1 NM_001287756.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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 (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.21T>C	p.Leu7Leu	synonymous_variant	Exon 1 of 8	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.21T>C	p.Leu7Leu	synonymous_variant	Exon 1 of 8	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29606 AN: 152180 Hom.: 3579 Cov.: 34

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.130 AC: 31689 AN: 243426 Hom.: 2571 AF XY: 0.128 AC XY: 16854 AN XY: 132112

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.0841

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0138

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0916

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.156 AC: 227142 AN: 1457954 Hom.: 19416 Cov.: 33 AF XY: 0.153 AC XY: 111263 AN XY: 725062

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.0900

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.195 AC: 29641 AN: 152298 Hom.: 3583 Cov.: 34 AF XY: 0.185 AC XY: 13813 AN XY: 74470

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0871

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.183

Alfa AF: 0.186 Hom.: 1608

Bravo AF: 0.203

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs1047643; hg19: chr8-11660362; COSMIC: COSV55043146; COSMIC: COSV55043146;