1-51832797-G-T

Variant names:

• chr1-51832797-G-T
• rs1417367
• NM_001101662.2:c.866+1220C>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.866+1220C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 152,102 control chromosomes in the GnomAD database, including 413 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 0.046 (413 hom., cov: 32)
• Consequence: NRDC NM_001101662.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.129 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.866+1220C>A		intron	N/A	NP_001095132.1	O43847-1
	NRDC	NM_002525.3		c.1070+1220C>A		intron	N/A	NP_002516.2	O43847-2
	NRDC	NM_001242361.2		c.674+1220C>A		intron	N/A	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.866+1220C>A		intron	N/A	ENSP00000262679.8	O43847-1
	NRDC	ENST00000354831.11	TSL:1	c.1070+1220C>A		intron	N/A	ENSP00000346890.7	O43847-2
	NRDC	ENST00000539524.5	TSL:1	c.674+1220C>A		intron	N/A	ENSP00000444416.1	G3V1R5

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7011 AN: 151984 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00837

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0463 AC: 7037 AN: 152102 Hom.: 413 Cov.: 32 AF XY: 0.0466 AC XY: 3466 AN XY: 74380

African (AFR) AF: 0.132 AC: 5481 AN: 41458

American (AMR) AF: 0.0147 AC: 225 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.0426 AC: 221 AN: 5186

South Asian (SAS) AF: 0.0977 AC: 471 AN: 4822

European-Finnish (FIN) AF: 0.000379 AC: 4 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00837 AC: 569 AN: 67998

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0170 Hom.: 29

Bravo AF: 0.0480

Asia WGS AF: 0.0710 AC: 244 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.28
PhyloP100		0.031
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: rs1417367; hg19: chr1-52298469;