chr1-51800570-G-A

Variant names:

• chr1-51800570-G-A
• rs8375
• NM_001101662.2:c.2427C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001101662.2(NRDC):​c.2427C>T​(p.Pro809Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,612,516 control chromosomes in the GnomAD database, including 210,959 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 0.46 (17446 hom., cov: 32)
  • Exomes 𝑓: 0.51 (193513 hom.)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101662.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDC	NM_001101662.2	MANE Select	c.2427C>T	p.Pro809Pro	synonymous	Exon 21 of 31	NP_001095132.1
	NRDC	NM_002525.3		c.2631C>T	p.Pro877Pro	synonymous	Exon 23 of 33	NP_002516.2
	NRDC	NM_001242361.2		c.2235C>T	p.Pro745Pro	synonymous	Exon 23 of 33	NP_001229290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDC	ENST00000352171.12	TSL:1 MANE Select	c.2427C>T	p.Pro809Pro	synonymous	Exon 21 of 31	ENSP00000262679.8
	NRDC	ENST00000354831.11	TSL:1	c.2631C>T	p.Pro877Pro	synonymous	Exon 23 of 33	ENSP00000346890.7
	NRDC	ENST00000539524.5	TSL:1	c.2235C>T	p.Pro745Pro	synonymous	Exon 23 of 33	ENSP00000444416.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69783 AN: 151804 Hom.: 17431 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.517 AC: 129783 AN: 250888 AF XY: 0.511

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.833

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.508 AC: 742312 AN: 1460594 Hom.: 193513 Cov.: 40 AF XY: 0.506 AC XY: 367337 AN XY: 726588

African (AFR) AF: 0.255 AC: 8521 AN: 33454

American (AMR) AF: 0.598 AC: 26688 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 12826 AN: 26122

East Asian (EAS) AF: 0.854 AC: 33889 AN: 39678

South Asian (SAS) AF: 0.417 AC: 35905 AN: 86140

European-Finnish (FIN) AF: 0.535 AC: 28592 AN: 53410

Middle Eastern (MID) AF: 0.400 AC: 2305 AN: 5762

European-Non Finnish (NFE) AF: 0.507 AC: 563246 AN: 1111024

Other (OTH) AF: 0.503 AC: 30340 AN: 60350

GnomAD4 genome AF: 0.460 AC: 69814 AN: 151922 Hom.: 17446 Cov.: 32 AF XY: 0.462 AC XY: 34293 AN XY: 74240

African (AFR) AF: 0.268 AC: 11091 AN: 41436

American (AMR) AF: 0.555 AC: 8457 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1744 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4314 AN: 5156

South Asian (SAS) AF: 0.419 AC: 2015 AN: 4810

European-Finnish (FIN) AF: 0.547 AC: 5755 AN: 10530

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34875 AN: 67960

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

Alfa AF: 0.498 Hom.: 52882

Bravo AF: 0.454

Asia WGS AF: 0.605 AC: 2102 AN: 3478

EpiCase AF: 0.510

EpiControl AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.2
DANN	Benign	0.51
PhyloP100		-3.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs8375; hg19: chr1-52266242; COSMIC: COSV61402584; COSMIC: COSV61402584;