1-51814574-C-A

Variant names:

• chr1-51814574-C-A
• NM_001101662.2:c.1596G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001101662.2(NRDC):​c.1596G>T​(p.Leu532Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRDC NM_001101662.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 1-51814574-C-A is Benign according to our data. Variant chr1-51814574-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3388842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.061 with no splicing effect.

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.1596G>T	p.Leu532Leu	synonymous	Exon 13 of 31	NP_001095132.1	O43847-1
	NRDC	NM_002525.3		c.1800G>T	p.Leu600Leu	synonymous	Exon 15 of 33	NP_002516.2	O43847-2
	NRDC	NM_001242361.2		c.1404G>T	p.Leu468Leu	synonymous	Exon 15 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.1596G>T	p.Leu532Leu	synonymous	Exon 13 of 31	ENSP00000262679.8	O43847-1
	NRDC	ENST00000354831.11	TSL:1	c.1800G>T	p.Leu600Leu	synonymous	Exon 15 of 33	ENSP00000346890.7	O43847-2
	NRDC	ENST00000539524.5	TSL:1	c.1404G>T	p.Leu468Leu	synonymous	Exon 15 of 33	ENSP00000444416.1	G3V1R5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr1-52280246;