1-155317450-G-C

Variant names:

• chr1-155317450-G-C
• rs17367421
• ENST00000543656.3:n.1256C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000543656.3(RUSC1-AS1):​n.1256C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 154,894 control chromosomes in the GnomAD database, including 116 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 0.035 (115 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1 hom.)
• Consequence: RUSC1-AS1 ENST00000543656.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 6 publications found

Genes affected

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

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: Genomics England PanelApp, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0348 (5300/152140) while in subpopulation NFE AF = 0.0468 (3184/67990). AF 95% confidence interval is 0.0455. There are 115 homozygotes in GnomAd4. There are 2627 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 115 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000543656.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDPS	NM_002004.4	MANE Select	c.481-491G>C		intron	N/A	NP_001995.1
	RUSC1-AS1	NR_145424.1		n.1183C>G		non_coding_transcript_exon	Exon 6 of 6
	RUSC1-AS1	NR_145425.1		n.908C>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUSC1-AS1	ENST00000543656.3	TSL:1	n.1256C>G		non_coding_transcript_exon	Exon 2 of 2
	FDPS	ENST00000368356.9	TSL:2 MANE Select	c.481-491G>C		intron	N/A	ENSP00000357340.4
	FDPS	ENST00000356657.10	TSL:1	c.481-491G>C		intron	N/A	ENSP00000349078.6

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5304 AN: 152022 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00981

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0353

GnomAD4 exome AF: 0.0225 AC: 62 AN: 2754 Hom.: 1 Cov.: 0 AF XY: 0.0237 AC XY: 34 AN XY: 1436

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.00932 AC: 6 AN: 644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 32

South Asian (SAS) AF: 0.00746 AC: 2 AN: 268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0313 AC: 53 AN: 1692

Other (OTH) AF: 0.0119 AC: 1 AN: 84

GnomAD4 genome AF: 0.0348 AC: 5300 AN: 152140 Hom.: 115 Cov.: 32 AF XY: 0.0353 AC XY: 2627 AN XY: 74364

African (AFR) AF: 0.00978 AC: 406 AN: 41506

American (AMR) AF: 0.0276 AC: 421 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4820

European-Finnish (FIN) AF: 0.0763 AC: 807 AN: 10578

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0468 AC: 3184 AN: 67990

Other (OTH) AF: 0.0350 AC: 74 AN: 2116

Alfa AF: 0.0169 Hom.: 6

Bravo AF: 0.0312

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.61
PhyloP100		-0.066
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: rs17367421; hg19: chr1-155287241;