1-155313038-A-G

Position:

• chr1-155313038-A-G

Variant summary

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

The NM_002004.4(FDPS):​c.480+643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,424 control chromosomes in the GnomAD database, including 14,282 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 0.40 (14281 hom., cov: 30)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: FDPS NM_002004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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]

FDPS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDPS	NM_002004.4	c.480+643A>G		intron_variant		ENST00000368356.9	NP_001995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDPS	ENST00000368356.9	c.480+643A>G		intron_variant		2	NM_002004.4	ENSP00000357340.4

Frequencies

GnomAD3 genomes AF: 0.396 AC: 59932 AN: 151286 Hom.: 14227 Cov.: 30

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.364 AC: 8 AN: 22 Hom.: 1 AF XY: 0.286 AC XY: 4 AN XY: 14

Gnomad4 AMR exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.397 AC: 60042 AN: 151402 Hom.: 14281 Cov.: 30 AF XY: 0.397 AC XY: 29369 AN XY: 73922

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.360

Alfa AF: 0.281 Hom.: 13955

Bravo AF: 0.416

Asia WGS AF: 0.551 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63

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: rs11264359; hg19: chr1-155282829;