chr1-51840391-ATCT-A

Position:

• chr1-51840391-ATCT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001101662.2(NRDC):​c.462_464del​(p.Glu154del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.24

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 -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/exons	MANE	UniProt
NRDC	NM_001101662.2	c.462_464del	p.Glu154del	inframe_deletion	2/31	ENST00000352171.12
NRDC	NM_001242361.2	c.66_68del	p.Glu22del	inframe_deletion	2/33
NRDC	NM_002525.3	c.462_464del	p.Glu154del	inframe_deletion	2/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRDC	ENST00000352171.12	c.462_464del	p.Glu154del	inframe_deletion	2/31	1	NM_001101662.2	P1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77007 AN: 151356 Hom.: 20811 Cov.: 0

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

GnomAD3 exomes AF: 0.572 AC: 141039 AN: 246606 Hom.: 42589 AF XY: 0.563 AC XY: 75166 AN XY: 133508

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 SAS exome AF: 0.470

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

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.943

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome AF: 0.509 AC: 77052 AN: 151472 Hom.: 20829 Cov.: 0 AF XY: 0.511 AC XY: 37799 AN XY: 73964

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.544

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs35723519; hg19: chr1-52306063;