1-51858556-C-T

Variant names:

• chr1-51858556-C-T
• rs2842576
• NM_001101662.2:c.342-18042G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101662.2(NRDC):​c.342-18042G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,106 control chromosomes in the GnomAD database, including 65,477 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 0.93 (65477 hom., cov: 30)
• Consequence: NRDC NM_001101662.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDC	NM_001101662.2	c.342-18042G>A		intron_variant	Intron 1 of 30	ENST00000352171.12	NP_001095132.1
NRDC	NM_002525.3	c.342-18042G>A		intron_variant	Intron 1 of 32		NP_002516.2
NRDC	NM_001242361.2	c.-55-18042G>A		intron_variant	Intron 1 of 32		NP_001229290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRDC	ENST00000352171.12	c.342-18042G>A		intron_variant	Intron 1 of 30	1	NM_001101662.2	ENSP00000262679.8
NRDC	ENST00000354831.11	c.342-18042G>A		intron_variant	Intron 1 of 32	1		ENSP00000346890.7
NRDC	ENST00000539524.5	c.-55-18042G>A		intron_variant	Intron 1 of 32	1		ENSP00000444416.1
NRDC	ENST00000491410.1	n.498-18042G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.928 AC: 140972 AN: 151990 Hom.: 65424 Cov.: 30

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.915

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.928 AC: 141081 AN: 152106 Hom.: 65477 Cov.: 30 AF XY: 0.929 AC XY: 69096 AN XY: 74354

African (AFR) AF: 0.913 AC: 37843 AN: 41442

American (AMR) AF: 0.928 AC: 14183 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3044 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.957 AC: 4603 AN: 4812

European-Finnish (FIN) AF: 0.966 AC: 10216 AN: 10580

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.927 AC: 63040 AN: 68014

Other (OTH) AF: 0.916 AC: 1935 AN: 2112

Alfa AF: 0.924 Hom.: 113825

Bravo AF: 0.923

Asia WGS AF: 0.969 AC: 3366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.35
PhyloP100		-0.76
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: rs2842576; hg19: chr1-52324228;