1-51825312-T-G

Variant names:

• chr1-51825312-T-G
• rs11205896
• NM_001101662.2:c.1011A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001101662.2(NRDC):​c.1011A>C​(p.Gly337Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,597,674 control chromosomes in the GnomAD database, including 207,619 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 (17583 hom., cov: 32)
  • Exomes 𝑓: 0.51 (190036 hom.)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.752
• Publications: 21 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.752 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDC	NM_001101662.2	MANE Select	c.1011A>C	p.Gly337Gly	synonymous	Exon 6 of 31	NP_001095132.1	O43847-1
	NRDC	NM_002525.3		c.1215A>C	p.Gly405Gly	synonymous	Exon 8 of 33	NP_002516.2	O43847-2
	NRDC	NM_001242361.2		c.819A>C	p.Gly273Gly	synonymous	Exon 8 of 33	NP_001229290.1	G3V1R5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRDC	ENST00000352171.12	TSL:1 MANE Select	c.1011A>C	p.Gly337Gly	synonymous	Exon 6 of 31	ENSP00000262679.8	O43847-1
	NRDC	ENST00000354831.11	TSL:1	c.1215A>C	p.Gly405Gly	synonymous	Exon 8 of 33	ENSP00000346890.7	O43847-2
	NRDC	ENST00000539524.5	TSL:1	c.819A>C	p.Gly273Gly	synonymous	Exon 8 of 33	ENSP00000444416.1	G3V1R5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70482 AN: 151890 Hom.: 17567 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.485

GnomAD2 exomes AF: 0.508 AC: 120895 AN: 237774 AF XY: 0.503

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.828

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.506 AC: 732227 AN: 1445666 Hom.: 190036 Cov.: 33 AF XY: 0.504 AC XY: 362374 AN XY: 719228

African (AFR) AF: 0.277 AC: 9010 AN: 32506

American (AMR) AF: 0.588 AC: 23993 AN: 40806

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12561 AN: 25780

East Asian (EAS) AF: 0.852 AC: 32983 AN: 38702

South Asian (SAS) AF: 0.414 AC: 34607 AN: 83572

European-Finnish (FIN) AF: 0.520 AC: 27696 AN: 53286

Middle Eastern (MID) AF: 0.408 AC: 1895 AN: 4642

European-Non Finnish (NFE) AF: 0.505 AC: 559264 AN: 1106648

Other (OTH) AF: 0.506 AC: 30218 AN: 59724

GnomAD4 genome AF: 0.464 AC: 70518 AN: 152008 Hom.: 17583 Cov.: 32 AF XY: 0.465 AC XY: 34579 AN XY: 74300

African (AFR) AF: 0.289 AC: 11969 AN: 41486

American (AMR) AF: 0.559 AC: 8547 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1733 AN: 3466

East Asian (EAS) AF: 0.837 AC: 4333 AN: 5178

South Asian (SAS) AF: 0.420 AC: 2022 AN: 4816

European-Finnish (FIN) AF: 0.530 AC: 5589 AN: 10538

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

European-Non Finnish (NFE) AF: 0.511 AC: 34727 AN: 67932

Other (OTH) AF: 0.491 AC: 1035 AN: 2110

Alfa AF: 0.464 Hom.: 6447

Bravo AF: 0.461

Asia WGS AF: 0.614 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs11205896; hg19: chr1-52290984; COSMIC: COSV61402651;