rs1770791

Variant names:

• chr1-51798392-A-G
• rs1770791
• NM_001101662.2:c.2461T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001101662.2(NRDC):​c.2461T>C​(p.Leu821Leu) 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
• Publications: 23 publications found

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]

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]

OSBPL9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000266993 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.15).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101662.2. 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
	NRDC	NM_001101662.2	MANE Select	c.2461T>C	p.Leu821Leu	synonymous	Exon 22 of 31	NP_001095132.1	O43847-1
	NRDC	NM_002525.3		c.2665T>C	p.Leu889Leu	synonymous	Exon 24 of 33	NP_002516.2	O43847-2
	NRDC	NM_001242361.2		c.2269T>C	p.Leu757Leu	synonymous	Exon 24 of 33	NP_001229290.1	G3V1R5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDC	ENST00000352171.12	TSL:1 MANE Select	c.2461T>C	p.Leu821Leu	synonymous	Exon 22 of 31	ENSP00000262679.8	O43847-1
	NRDC	ENST00000354831.11	TSL:1	c.2665T>C	p.Leu889Leu	synonymous	Exon 24 of 33	ENSP00000346890.7	O43847-2
	NRDC	ENST00000539524.5	TSL:1	c.2269T>C	p.Leu757Leu	synonymous	Exon 24 of 33	ENSP00000444416.1	G3V1R5

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

GnomAD2 exomes AF: 0.281 AC: 70448 AN: 250928 AF XY: 0.270

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 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

African (AFR) AF: 0.618 AC: 20686 AN: 33454

American (AMR) AF: 0.406 AC: 18161 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8820 AN: 26122

East Asian (EAS) AF: 0.153 AC: 6081 AN: 39692

South Asian (SAS) AF: 0.243 AC: 20948 AN: 86214

European-Finnish (FIN) AF: 0.136 AC: 7264 AN: 53398

Middle Eastern (MID) AF: 0.417 AC: 2406 AN: 5766

European-Non Finnish (NFE) AF: 0.236 AC: 262502 AN: 1111032

Other (OTH) AF: 0.268 AC: 16172 AN: 60366

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

African (AFR) AF: 0.602 AC: 24935 AN: 41410

American (AMR) AF: 0.340 AC: 5183 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3466

East Asian (EAS) AF: 0.166 AC: 862 AN: 5178

South Asian (SAS) AF: 0.250 AC: 1202 AN: 4812

European-Finnish (FIN) AF: 0.128 AC: 1354 AN: 10592

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16027 AN: 67996

Other (OTH) AF: 0.331 AC: 698 AN: 2110

Alfa AF: 0.282 Hom.: 13717

Bravo AF: 0.373

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.68
PhyloP100		1.8
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: rs1770791; hg19: chr1-52264064; COSMIC: COSV61404414; COSMIC: COSV61404414;