Variant 1-51878485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001101662.2(NRDC):c.131C>T(p.Pro44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,613,946 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 12 hom. )

Consequence

NRDC
NM_001101662.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.505

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023062527).

BP6

Variant 1-51878485-G-A is Benign according to our data. Variant chr1-51878485-G-A is described in ClinVar as [Benign]. Clinvar id is 711769.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00479 (729/152290) while in subpopulation AFR AF= 0.0171 (710/41546). AF 95% confidence interval is 0.016. There are 7 homozygotes in gnomad4. There are 338 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 729 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDC	NM_001101662.2 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 1 of 31	ENST00000352171.12	NP_001095132.1	O43847-1Q6UUU9
NRDC	NM_002525.3 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 1 of 33		NP_002516.2	O43847-2Q6UUU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NRDC	ENST00000352171.12 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 1 of 31	1	NM_001101662.2	ENSP00000262679.8	O43847-1
NRDC	ENST00000354831.11 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 1 of 33	1		ENSP00000346890.7	O43847-2
NRDC	ENST00000468722.1 link	n.239C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
NRDC	ENST00000491410.1 link	n.287C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

731

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00139

AC:

348

AN:

250968

Hom.:

AF XY:

0.000870

AC XY:

118

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.0191

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000513

AC:

750

AN:

1461656

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

289

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.00479

AC:

729

AN:

152290

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000921

Hom.:

Bravo

AF:

0.00615

ESP6500AA

AF:

0.0163

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00156

AC:

190

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.81

N;N;.

REVEL

Benign

0.019

Sift

Benign

0.23

T;T;.

Sift4G

Benign

0.36

T;T;T

Polyphen

0.19

B;.;.

Vest4

0.083

MVP

0.043

MPC

0.099

ClinPred

0.016

GERP RS

3.3

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.051

gMVP

0.28

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over