rs3135499

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

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

Conservation

PhyloP100: -0.931
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]
CYLD-AS1 (HGNC:55352): (CYLD antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons MANE Protein UniProt
NOD2NM_001370466.1 linkuse as main transcriptc.*397A>C 3_prime_UTR_variant 12/12 ENST00000647318.2 NP_001357395.1
CYLD-AS1NR_184279.1 linkuse as main transcriptn.412+2T>G splice_donor_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOD2ENST00000647318.2 linkuse as main transcriptc.*397A>C 3_prime_UTR_variant 12/12 NM_001370466.1 ENSP00000495993 P1Q9HC29-2
CYLD-AS1ENST00000563315.2 linkuse as main transcriptn.1013+2T>G splice_donor_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.445
AC:
67416
AN:
151636
Hom.:
15619
Cov.:
30
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.:
0
AF XY:
0.363
AC XY:
39328
AN XY:
108376
show subpopulations
Gnomad4 AFR exome
AF:
0.561
Gnomad4 AMR exome
AF:
0.353
Gnomad4 ASJ exome
AF:
0.525
Gnomad4 EAS exome
AF:
0.219
Gnomad4 SAS exome
AF:
0.253
Gnomad4 FIN exome
AF:
0.427
Gnomad4 NFE exome
AF:
0.408
Gnomad4 OTH exome
AF:
0.399
GnomAD4 genome
AF:
0.445
AC:
67495
AN:
151754
Hom.:
15644
Cov.:
30
AF XY:
0.440
AC XY:
32618
AN XY:
74162
show subpopulations
Gnomad4 AFR
AF:
0.556
Gnomad4 AMR
AF:
0.404
Gnomad4 ASJ
AF:
0.532
Gnomad4 EAS
AF:
0.189
Gnomad4 SAS
AF:
0.228
Gnomad4 FIN
AF:
0.432
Gnomad4 NFE
AF:
0.419
Gnomad4 OTH
AF:
0.411
Alfa
AF:
0.417
Hom.:
27852
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
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Inflammatory bowel disease 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
Leprosy, susceptibility to, 1 Other:1
Uncertain risk allele, no assertion criteria providedcase-controlCentro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras AcostaJun 10, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
9.3
DANN
Benign
0.37

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.

Other links and lift over

dbSNP: rs3135499; hg19: chr16-50766127; COSMIC: COSV56051520; COSMIC: COSV56051520; API