chr16-50732216-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001370466.1(NOD2):c.*397A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 353,018 control chromosomes in the GnomAD database, including 30,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15644 hom., cov: 30)

Exomes 𝑓: 0.38 ( 15321 hom. )

Consequence

NOD2
NM_001370466.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.931

Publications

48 publications found

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:

CYLD-AS1 (HGNC:55352): (CYLD antisense RNA 1)

CYLD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-50732216-A-C is Benign according to our data. Variant chr16-50732216-A-C is described in ClinVar as Benign. ClinVar VariationId is 319482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1 link	c.*397A>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2 link	c.*397A>C		3_prime_UTR_variant	Exon 12 of 12		NM_001370466.1	ENSP00000495993.1		Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67416

AN:

151636

Hom.:

15619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.416

GnomAD4 exome

AF:

0.377

AC:

75867

AN:

201264

Hom.:

15321

Cov.:

AF XY:

0.363

AC XY:

39328

AN XY:

108376

show subpopulations

African (AFR)

AF:

0.561

AC:

3310

AN:

5904

American (AMR)

AF:

0.353

AC:

3612

AN:

10218

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

2645

AN:

5036

East Asian (EAS)

AF:

0.219

AC:

2209

AN:

10090

South Asian (SAS)

AF:

0.253

AC:

8859

AN:

35056

European-Finnish (FIN)

AF:

0.427

AC:

4339

AN:

10170

Middle Eastern (MID)

AF:

0.429

AC:

310

AN:

722

European-Non Finnish (NFE)

AF:

0.408

AC:

46494

AN:

113824

Other (OTH)

AF:

0.399

AC:

4089

AN:

10244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

2113

4226

6340

8453

10566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.445

AC:

67495

AN:

151754

Hom.:

15644

Cov.:

AF XY:

0.440

AC XY:

32618

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.556

AC:

23006

AN:

41354

American (AMR)

AF:

0.404

AC:

6163

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

1845

AN:

3470

East Asian (EAS)

AF:

0.189

AC:

970

AN:

5128

South Asian (SAS)

AF:

0.228

AC:

1095

AN:

4812

European-Finnish (FIN)

AF:

0.432

AC:

4550

AN:

10542

Middle Eastern (MID)

AF:

0.380

AC:

111

AN:

292

European-Non Finnish (NFE)

AF:

0.419

AC:

28417

AN:

67894

Other (OTH)

AF:

0.411

AC:

863

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1842

3684

5525

7367

9209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.422

Hom.:

59568

Bravo

AF:

0.448

Asia WGS

AF:

0.235

AC:

816

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inflammatory bowel disease 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leprosy, susceptibility to, 1

Other:1

Jun 10, 2022

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Significance:Uncertain risk allele

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

9.3

(source)

DANN

Benign

0.37

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over