chr1-155319754-T-G

Variant names:

• chr1-155319754-T-G
• rs11264361
• NM_002004.4:c.925-40T>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002004.4(FDPS):​c.925-40T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,613,438 control chromosomes in the GnomAD database, including 65,708 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.27 (6093 hom., cov: 32)
  • Exomes 𝑓: 0.27 (59615 hom.)
• Consequence: FDPS NM_002004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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]

RUSC1-AS1 (HGNC:26680): (RUSC1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDPS	NM_002004.4	c.925-40T>G		intron_variant	Intron 9 of 10	ENST00000368356.9	NP_001995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDPS	ENST00000368356.9	c.925-40T>G		intron_variant	Intron 9 of 10	2	NM_002004.4	ENSP00000357340.4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40945 AN: 151966 Hom.: 6084 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.274

GnomAD3 exomes AF: 0.309 AC: 77582 AN: 251396 Hom.: 14118 AF XY: 0.302 AC XY: 41021 AN XY: 135854

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.722

Gnomad SAS exome AF: 0.302

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.277

GnomAD4 exome AF: 0.271 AC: 396465 AN: 1461354 Hom.: 59615 Cov.: 35 AF XY: 0.270 AC XY: 196282 AN XY: 726960

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.743

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.269 AC: 40969 AN: 152084 Hom.: 6093 Cov.: 32 AF XY: 0.274 AC XY: 20364 AN XY: 74348

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.270

Alfa AF: 0.237 Hom.: 4522

Bravo AF: 0.273

Asia WGS AF: 0.498 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.74
BranchPoint Hunter		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs11264361; hg19: chr1-155289545;