rs1736058

chr8-11813532-G-A

Variant summary

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

The NM_004462.5(FDFT1):c.381+3682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,096 control chromosomes in the GnomAD database, including 2,935 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 0.18 (2935 hom., cov: 32)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.381+3682G>A		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.381+3682G>A		intron_variant		1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27753 AN: 151980 Hom.: 2938 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.183 AC: 27773 AN: 152096 Hom.: 2935 Cov.: 32 AF XY: 0.189 AC XY: 14034 AN XY: 74346

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.188

Alfa AF: 0.193 Hom.: 6300

Bravo AF: 0.179

Asia WGS AF: 0.331 AC: 1147 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	0.63
Dann	Benign	0.51

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: rs1736058; hg19: chr8-11671041;