Variant chr1-51878439-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001101662.2(NRDC):c.177C>T(p.Thr59=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00157 in 1,614,092 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 13 hom. )

Consequence

NRDC
NM_001101662.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.60

Variant links:

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]

NRDC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-51878439-G-A is Benign according to our data. Variant chr1-51878439-G-A is described in ClinVar as [Benign]. Clinvar id is 780238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0084 (1280/152312) while in subpopulation AFR AF= 0.0297 (1234/41562). AF 95% confidence interval is 0.0283. There are 18 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRDC	NM_001101662.2 linkuse as main transcript	c.177C>T	p.Thr59=	synonymous_variant	1/31	ENST00000352171.12	NP_001095132.1
NRDC	NM_002525.3 linkuse as main transcript	c.177C>T	p.Thr59=	synonymous_variant	1/33		NP_002516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRDC	ENST00000352171.12 linkuse as main transcript	c.177C>T	p.Thr59=	synonymous_variant	1/31	1	NM_001101662.2	ENSP00000262679	P1	O43847-1
NRDC	ENST00000354831.11 linkuse as main transcript	c.177C>T	p.Thr59=	synonymous_variant	1/33	1		ENSP00000346890		O43847-2
NRDC	ENST00000468722.1 linkuse as main transcript	n.285C>T		non_coding_transcript_exon_variant	1/2	3
NRDC	ENST00000491410.1 linkuse as main transcript	n.333C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1274

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00220

AC:

553

AN:

251318

Hom.:

AF XY:

0.00167

AC XY:

227

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0311

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000862

AC:

1260

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

537

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000890

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00840

AC:

1280

AN:

152312

Hom.:

Cov.:

AF XY:

0.00843

AC XY:

628

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0297

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.00938

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.9

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over