Variant rs2273198 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.925

Variant links:

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]

NRDC links:

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ACMG classification

Classification made for transcript

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
NRDC	NM_001101662.2 linkuse as main transcript	c.2319G>A	p.Leu773=	synonymous_variant	21/31	ENST00000352171.12
NRDC	NM_002525.3 linkuse as main transcript	c.2523G>A	p.Leu841=	synonymous_variant	23/33
NRDC	NM_001242361.2 linkuse as main transcript	c.2127G>A	p.Leu709=	synonymous_variant	23/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRDC	ENST00000352171.12 linkuse as main transcript	c.2319G>A	p.Leu773=	synonymous_variant	21/31	1	NM_001101662.2	P1	O43847-1

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6749

AN:

152062

Hom.:

209

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0329

AC XY:

23857

AN XY:

725902

show subpopulations

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.:

AF XY:

0.0455

AC XY:

3385

AN XY:

74400

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over