Genetic Variant NRDC:p.Glu154del (chr1-51840391-ATCT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001101662.2(NRDC):c.462_464delAGA(p.Glu154del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,534,630 control chromosomes in the GnomAD database, including 227,291 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.51 ( 20829 hom., cov: 0)

Exomes 𝑓: 0.54 ( 206462 hom. )

Consequence

NRDC
NM_001101662.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.24

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-51840391-ATCT-A is Benign according to our data. Variant chr1-51840391-ATCT-A is described in ClinVar as [Benign]. Clinvar id is 1331177.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDC	NM_001101662.2 link	c.462_464delAGA	p.Glu154del	disruptive_inframe_deletion	Exon 2 of 31	ENST00000352171.12	NP_001095132.1	O43847-1Q6UUU9
NRDC	NM_002525.3 link	c.462_464delAGA	p.Glu154del	disruptive_inframe_deletion	Exon 2 of 33		NP_002516.2	O43847-2Q6UUU9
NRDC	NM_001242361.2 link	c.66_68delAGA	p.Glu22del	disruptive_inframe_deletion	Exon 2 of 33		NP_001229290.1	O43847G3V1R5Q6UUU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRDC	ENST00000352171.12 link	c.462_464delAGA	p.Glu154del	disruptive_inframe_deletion	Exon 2 of 31	1	NM_001101662.2	ENSP00000262679.8		O43847-1

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77007

AN:

151356

Hom.:

20811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.935

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.535

Gnomad OTH

AF:

0.539

GnomAD2 exomes

AF:

0.572

AC:

141039

AN:

246606

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.719

Gnomad ASJ exome

AF:

0.613

Gnomad EAS exome

AF:

0.942

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.530

Gnomad OTH exome

AF:

0.570

GnomAD4 exome

AF:

0.537

AC:

742132

AN:

1383158

Hom.:

206462

AF XY:

0.535

AC XY:

370477

AN XY:

692366

show subpopulations

Gnomad4 AFR exome

AF:

0.343

AC:

11000

AN:

32098

Gnomad4 AMR exome

AF:

0.712

AC:

31654

AN:

44468

Gnomad4 ASJ exome

AF:

0.614

AC:

15743

AN:

25624

Gnomad4 EAS exome

AF:

0.943

AC:

36978

AN:

39210

Gnomad4 SAS exome

AF:

0.471

AC:

39802

AN:

84590

Gnomad4 FIN exome

AF:

0.527

AC:

28074

AN:

53260

Gnomad4 NFE exome

AF:

0.523

AC:

544265

AN:

1040430

Gnomad4 Remaining exome

AF:

0.547

AC:

31665

AN:

57848

Heterozygous variant carriers

15667

31334

47001

62668

78335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

15136

30272

45408

60544

75680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.509

AC:

77052

AN:

151472

Hom.:

20829

Cov.:

AF XY:

0.511

AC XY:

37799

AN XY:

73964

show subpopulations

Gnomad4 AFR

AF:

0.346

AC:

0.346459

AN:

0.346459

Gnomad4 AMR

AF:

0.646

AC:

0.64637

AN:

0.64637

Gnomad4 ASJ

AF:

0.623

AC:

0.623272

AN:

0.623272

Gnomad4 EAS

AF:

0.935

AC:

0.934639

AN:

0.934639

Gnomad4 SAS

AF:

0.474

AC:

0.473509

AN:

0.473509

Gnomad4 FIN

AF:

0.537

AC:

0.536775

AN:

0.536775

Gnomad4 NFE

AF:

0.535

AC:

0.535338

AN:

0.535338

Gnomad4 OTH

AF:

0.544

AC:

0.544061

AN:

0.544061

Heterozygous variant carriers

1753

3507

5260

7014

8767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.453

Hom.:

2095

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 29, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=76/24

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

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