rs1770791

chr1-51798392-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001101662.2(NRDC):c.2461T>C(p.Leu821=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,612,772 control chromosomes in the GnomAD database, including 60,235 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 0.34 (11023 hom., cov: 31)
  • Exomes 𝑓: 0.25 (49212 hom.)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

NRDC (HGNC:7995): (nardilysin convertase) This gene encodes a zinc-dependent endopeptidase that cleaves peptide substrates at the N-terminus of arginine residues in dibasic moieties and is a member of the peptidase M16 family. This protein interacts with heparin-binding EGF-like growth factor and plays a role in cell migration and proliferation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

(HGNC:):

OSBPL9 (HGNC:16386): (oxysterol binding protein like 9) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. This family member functions as a cholesterol transfer protein that regulates Golgi structure and function. Multiple transcript variants, most of which encode distinct isoforms, have been identified. Related pseudogenes have been identified on chromosomes 3, 11 and 12. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRDC	NM_001101662.2	c.2461T>C	p.Leu821=	synonymous_variant	22/31	ENST00000352171.12
NRDC	NM_002525.3	c.2665T>C	p.Leu889=	synonymous_variant	24/33
NRDC	NM_001242361.2	c.2269T>C	p.Leu757=	synonymous_variant	24/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRDC	ENST00000352171.12	c.2461T>C	p.Leu821=	synonymous_variant	22/31	1	NM_001101662.2	P1
	ENST00000586761.2	n.528A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51648 AN: 151914 Hom.: 10978 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.334

GnomAD3 exomes AF: 0.281 AC: 70448 AN: 250928 Hom.: 11592 AF XY: 0.270 AC XY: 36681 AN XY: 135628

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.185

Gnomad SAS exome AF: 0.243

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.283

GnomAD4 exome AF: 0.249 AC: 363040 AN: 1460740 Hom.: 49212 Cov.: 32 AF XY: 0.247 AC XY: 179694 AN XY: 726722

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.340 AC: 51738 AN: 152032 Hom.: 11023 Cov.: 31 AF XY: 0.335 AC XY: 24929 AN XY: 74342

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.331

Alfa AF: 0.273 Hom.: 10419

Bravo AF: 0.373

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	17
Dann	Benign	0.68

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: rs1770791; hg19: chr1-52264064; COSMIC: COSV61404414; COSMIC: COSV61404414;