8-11810644-T-C

Variant names:

• chr8-11810644-T-C
• rs1534863
• NM_004462.5:c.381+794T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004462.5(FDFT1):​c.381+794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,150 control chromosomes in the GnomAD database, including 3,138 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 0.19 (3138 hom., cov: 32)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.381+794T>C		intron_variant	Intron 3 of 7	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.381+794T>C		intron_variant	Intron 3 of 7	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28940 AN: 152032 Hom.: 3142 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.190 AC: 28952 AN: 152150 Hom.: 3138 Cov.: 32 AF XY: 0.197 AC XY: 14625 AN XY: 74388

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.208

Alfa AF: 0.197 Hom.: 1357

Bravo AF: 0.189

Asia WGS AF: 0.335 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1534863; hg19: chr8-11668153;