chr16-50699948-C-G

Position:

chr16-50699948-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370466.1(NOD2):c.453C>G(p.Ser151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,604,806 control chromosomes in the GnomAD database, including 115,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10039 hom., cov: 31)

Exomes 𝑓: 0.37 ( 105338 hom. )

Consequence

NOD2
NM_001370466.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.355

Variant links:

Genes affected

NOD2 (HGNC:5331): (nucleotide binding oligomerization domain containing 2) This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

NOD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 16-50699948-C-G is Benign according to our data. Variant chr16-50699948-C-G is described in ClinVar as [Benign]. Clinvar id is 319429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-50699948-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.355 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD2	NM_001370466.1 linkuse as main transcript	c.453C>G	p.Ser151=	synonymous_variant	2/12	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.453C>G	p.Ser151=	synonymous_variant	2/12		NM_001370466.1	ENSP00000495993	P1	Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53564

AN:

151888

Hom.:

10040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.331

AC:

80774

AN:

243838

Hom.:

15100

AF XY:

0.334

AC XY:

44159

AN XY:

132224

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.0592

Gnomad SAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.372

AC:

540163

AN:

1452798

Hom.:

105338

Cov.:

AF XY:

0.369

AC XY:

266990

AN XY:

722980

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.0566

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.394

Gnomad4 OTH exome

AF:

0.364

GnomAD4 genome

AF:

0.352

AC:

53566

AN:

152008

Hom.:

10039

Cov.:

AF XY:

0.349

AC XY:

25966

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.346

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.0516

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.434

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.352

Alfa

AF:

0.321

Hom.:

1513

Bravo

AF:

0.342

Asia WGS

AF:

0.141

AC:

491

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.405

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Regional enteritis;C5201146:Blau syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inflammatory bowel disease 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Blau syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.6

DANN

Benign

0.58

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