chr1-51800678-C-T

Variant names:

• chr1-51800678-C-T
• rs2273198
• NM_001101662.2:c.2319G>A

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.2319G>A​(p.Leu773Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,611,502 control chromosomes in the GnomAD database, including 1,550 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. Synonymous variant affecting the same amino acid position (i.e. L773L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.044 (209 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1341 hom.)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 13 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 (REVEL=0.039).
• BP7: Synonymous conserved (PhyloP=-0.925 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0876 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.2319G>A	p.Leu773Leu	synonymous	Exon 21 of 31	NP_001095132.1	O43847-1
	NRDC	NM_002525.3		c.2523G>A	p.Leu841Leu	synonymous	Exon 23 of 33	NP_002516.2	O43847-2
	NRDC	NM_001242361.2		c.2127G>A	p.Leu709Leu	synonymous	Exon 23 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.2319G>A	p.Leu773Leu	synonymous	Exon 21 of 31	ENSP00000262679.8	O43847-1
	NRDC	ENST00000354831.11	TSL:1	c.2523G>A	p.Leu841Leu	synonymous	Exon 23 of 33	ENSP00000346890.7	O43847-2
	NRDC	ENST00000539524.5	TSL:1	c.2127G>A	p.Leu709Leu	synonymous	Exon 23 of 33	ENSP00000444416.1	G3V1R5

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6749 AN: 152062 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.00813

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0550

GnomAD2 exomes AF: 0.0534 AC: 13304 AN: 249032 AF XY: 0.0511

Gnomad AFR exome AF: 0.0553

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.00643

Gnomad NFE exome AF: 0.0260

Gnomad OTH exome AF: 0.0524

GnomAD4 exome AF: 0.0319 AC: 46625 AN: 1459322 Hom.: 1341 Cov.: 31 AF XY: 0.0329 AC XY: 23857 AN XY: 725902

African (AFR) AF: 0.0622 AC: 2075 AN: 33362

American (AMR) AF: 0.112 AC: 4944 AN: 44250

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3278 AN: 26062

East Asian (EAS) AF: 0.0879 AC: 3485 AN: 39652

South Asian (SAS) AF: 0.0560 AC: 4797 AN: 85594

European-Finnish (FIN) AF: 0.00700 AC: 374 AN: 53406

Middle Eastern (MID) AF: 0.115 AC: 659 AN: 5746

European-Non Finnish (NFE) AF: 0.0220 AC: 24455 AN: 1110968

Other (OTH) AF: 0.0424 AC: 2558 AN: 60282

GnomAD4 genome AF: 0.0444 AC: 6755 AN: 152180 Hom.: 209 Cov.: 32 AF XY: 0.0455 AC XY: 3385 AN XY: 74400

African (AFR) AF: 0.0570 AC: 2369 AN: 41528

American (AMR) AF: 0.0854 AC: 1304 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3466

East Asian (EAS) AF: 0.0945 AC: 488 AN: 5164

South Asian (SAS) AF: 0.0575 AC: 278 AN: 4832

European-Finnish (FIN) AF: 0.00813 AC: 86 AN: 10584

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0240 AC: 1634 AN: 68022

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0379 Hom.: 322

Bravo AF: 0.0511

Asia WGS AF: 0.0750 AC: 263 AN: 3478

EpiCase AF: 0.0318

EpiControl AF: 0.0302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		-0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs2273198; hg19: chr1-52266350; COSMIC: COSV61407819; COSMIC: COSV61407819;