1-155313038-A-G

Variant names:

• chr1-155313038-A-G
• rs11264359
• NM_002004.4:c.480+643A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 publications found

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 Gene-Disease associations (from GenCC):

• porokeratosis 9, multiple types

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• disseminated superficial actinic porokeratosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002004.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDPS	NM_002004.4	MANE Select	c.480+643A>G		intron	N/A	NP_001995.1	P14324-1
	FDPS	NM_001135821.2		c.480+643A>G		intron	N/A	NP_001129293.1	P14324-1
	FDPS	NM_001135822.2		c.282+643A>G		intron	N/A	NP_001129294.1	P14324-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDPS	ENST00000368356.9	TSL:2 MANE Select	c.480+643A>G		intron	N/A	ENSP00000357340.4	P14324-1
	FDPS	ENST00000356657.10	TSL:1	c.480+643A>G		intron	N/A	ENSP00000349078.6	P14324-1
	FDPS	ENST00000851541.1		c.480+643A>G		intron	N/A	ENSP00000521600.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 6 AN: 18

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.652 AC: 26803 AN: 41118

American (AMR) AF: 0.332 AC: 5060 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3470

East Asian (EAS) AF: 0.723 AC: 3733 AN: 5164

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4812

European-Finnish (FIN) AF: 0.313 AC: 3243 AN: 10358

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17845 AN: 67942

Other (OTH) AF: 0.360 AC: 756 AN: 2100

Alfa AF: 0.305 Hom.: 36971

Bravo AF: 0.416

Asia WGS AF: 0.551 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11264359; hg19: chr1-155282829;