rs8375

chr1-51800570-G-Achr1-51800570-G-Cchr1-51800570-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001101662.2(NRDC):c.2427C>T(p.Pro809=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,612,516 control chromosomes in the GnomAD database, including 210,959 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 0.46 (17446 hom., cov: 32)
  • Exomes 𝑓: 0.51 (193513 hom.)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRDC	NM_001101662.2	c.2427C>T	p.Pro809=	synonymous_variant	21/31	ENST00000352171.12
NRDC	NM_002525.3	c.2631C>T	p.Pro877=	synonymous_variant	23/33
NRDC	NM_001242361.2	c.2235C>T	p.Pro745=	synonymous_variant	23/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRDC	ENST00000352171.12	c.2427C>T	p.Pro809=	synonymous_variant	21/31	1	NM_001101662.2	P1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69783 AN: 151804 Hom.: 17431 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.476

GnomAD3 exomes AF: 0.517 AC: 129783 AN: 250888 Hom.: 35473 AF XY: 0.511 AC XY: 69282 AN XY: 135596

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.833

Gnomad SAS exome AF: 0.412

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.508 AC: 742312 AN: 1460594 Hom.: 193513 Cov.: 40 AF XY: 0.506 AC XY: 367337 AN XY: 726588

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.460 AC: 69814 AN: 151922 Hom.: 17446 Cov.: 32 AF XY: 0.462 AC XY: 34293 AN XY: 74240

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.481

Alfa AF: 0.495 Hom.: 18406

Bravo AF: 0.454

Asia WGS AF: 0.605 AC: 2102 AN: 3478

EpiCase AF: 0.510

EpiControl AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	3.2
Dann	Benign	0.51
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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: rs8375; hg19: chr1-52266242; COSMIC: COSV61402584; COSMIC: COSV61402584;