1-155309691-T-G

Position:

• chr1-155309691-T-G

Variant summary

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

The NM_002004.4(FDPS):​c.-1-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,103,806 control chromosomes in the GnomAD database, including 46,879 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 0.29 (6847 hom., cov: 31)
  • Exomes 𝑓: 0.27 (40032 hom.)
• Consequence: FDPS NM_002004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

Genes affected

FDPS (HGNC:3631): (farnesyl diphosphate synthase) This gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDPS	NM_002004.4	c.-1-98T>G		intron_variant		ENST00000368356.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDPS	ENST00000368356.9	c.-1-98T>G		intron_variant		2	NM_002004.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43742 AN: 151904 Hom.: 6833 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.273 AC: 259665 AN: 951786 Hom.: 40032 Cov.: 12 AF XY: 0.272 AC XY: 127091 AN XY: 467952

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.288 AC: 43774 AN: 152020 Hom.: 6847 Cov.: 31 AF XY: 0.291 AC XY: 21602 AN XY: 74318

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.284

Alfa AF: 0.240 Hom.: 4331

Bravo AF: 0.294

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.47

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: rs2297480; hg19: chr1-155279482; COSMIC: COSV63115029;