8-11826954-A-G

Position:

• chr8-11826954-A-G

Variant summary

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

The NM_004462.5(FDFT1):​c.702+739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,074 control chromosomes in the GnomAD database, including 23,903 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 0.55 (23903 hom., cov: 33)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.702+739A>G		intron_variant		ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.702+739A>G		intron_variant		1	NM_004462.5	ENSP00000220584	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84327 AN: 151956 Hom.: 23894 Cov.: 33

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.555 AC: 84379 AN: 152074 Hom.: 23903 Cov.: 33 AF XY: 0.551 AC XY: 40954 AN XY: 74330

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.560

Alfa AF: 0.586 Hom.: 58306

Bravo AF: 0.552

Asia WGS AF: 0.429 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.16

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: rs2645424; hg19: chr8-11684463;