rs2273198

chr1-51800678-C-T

Variant summary

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

The NM_001101662.2(NRDC):c.2319G>A(p.Leu773=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,611,502 control chromosomes in the GnomAD database, including 1,550 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 0.044 (209 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1341 hom.)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=-0.925 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRDC	NM_001101662.2	c.2319G>A	p.Leu773=	synonymous_variant	21/31	ENST00000352171.12
NRDC	NM_002525.3	c.2523G>A	p.Leu841=	synonymous_variant	23/33
NRDC	NM_001242361.2	c.2127G>A	p.Leu709=	synonymous_variant	23/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRDC	ENST00000352171.12	c.2319G>A	p.Leu773=	synonymous_variant	21/31	1	NM_001101662.2	P1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6749 AN: 152062 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.00813

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0550

GnomAD3 exomes AF: 0.0534 AC: 13304 AN: 249032 Hom.: 582 AF XY: 0.0511 AC XY: 6881 AN XY: 134560

Gnomad AFR exome AF: 0.0553

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.0581

Gnomad FIN exome AF: 0.00643

Gnomad NFE exome AF: 0.0260

Gnomad OTH exome AF: 0.0524

GnomAD4 exome AF: 0.0319 AC: 46625 AN: 1459322 Hom.: 1341 Cov.: 31 AF XY: 0.0329 AC XY: 23857 AN XY: 725902

Gnomad4 AFR exome AF: 0.0622

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0879

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.00700

Gnomad4 NFE exome AF: 0.0220

Gnomad4 OTH exome AF: 0.0424

GnomAD4 genome AF: 0.0444 AC: 6755 AN: 152180 Hom.: 209 Cov.: 32 AF XY: 0.0455 AC XY: 3385 AN XY: 74400

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.0854

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.0575

Gnomad4 FIN AF: 0.00813

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0370 Hom.: 229

Bravo AF: 0.0511

Asia WGS AF: 0.0750 AC: 263 AN: 3478

EpiCase AF: 0.0318

EpiControl AF: 0.0302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	2.0
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2273198; hg19: chr1-52266350; COSMIC: COSV61407819; COSMIC: COSV61407819;