1-51871367-T-C

Variant names:

• chr1-51871367-T-C
• rs1538881
• NM_001101662.2:c.341+6908A>G

Variant summary

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

The NM_001101662.2(NRDC):​c.341+6908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,370 control chromosomes in the GnomAD database, including 21,115 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 0.51 (21115 hom., cov: 27)
• Consequence: NRDC NM_001101662.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDC	NM_001101662.2	c.341+6908A>G		intron_variant	Intron 1 of 30	ENST00000352171.12	NP_001095132.1
NRDC	NM_002525.3	c.341+6908A>G		intron_variant	Intron 1 of 32		NP_002516.2
NRDC	NM_001242361.2	c.-56+6616A>G		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.341+6908A>G		intron_variant	Intron 1 of 30	1	NM_001101662.2	ENSP00000262679.8

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77470 AN: 151252 Hom.: 21096 Cov.: 27

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.512 AC: 77518 AN: 151370 Hom.: 21115 Cov.: 27 AF XY: 0.515 AC XY: 38050 AN XY: 73940

African (AFR) AF: 0.348 AC: 14354 AN: 41204

American (AMR) AF: 0.649 AC: 9871 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2182 AN: 3462

East Asian (EAS) AF: 0.935 AC: 4809 AN: 5142

South Asian (SAS) AF: 0.477 AC: 2277 AN: 4778

European-Finnish (FIN) AF: 0.540 AC: 5645 AN: 10450

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36601 AN: 67824

Other (OTH) AF: 0.548 AC: 1154 AN: 2106

Alfa AF: 0.527 Hom.: 11031

Bravo AF: 0.516

Asia WGS AF: 0.695 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		-0.29
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: rs1538881; hg19: chr1-52337039; COSMIC: COSV61402994;