rs34133110

Variant names:

• chr16-50710008-C-T
• rs34133110
• ENST00000526417.6:n.698C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000526417.6(NOD2):​n.698C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 455,762 control chromosomes in the GnomAD database, including 28,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8839 hom., cov: 32)
  • Exomes 𝑓: 0.35 (19802 hom.)
• Consequence: NOD2 ENST00000526417.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.563
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• Blau syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Genomics England PanelApp, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• inflammatory bowel disease 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-50710008-C-T is Benign according to our data. Variant chr16-50710008-C-T is described in ClinVar as [Benign]. Clinvar id is 2688030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.566-550C>T		intron_variant	Intron 3 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.566-550C>T		intron_variant	Intron 3 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49467 AN: 151966 Hom.: 8843 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.345

GnomAD2 exomes AF: 0.326 AC: 41720 AN: 128010 AF XY: 0.325

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.150

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.347 AC: 105379 AN: 303676 Hom.: 19802 Cov.: 0 AF XY: 0.339 AC XY: 58702 AN XY: 172938

African (AFR) AF: 0.189 AC: 1627 AN: 8616

American (AMR) AF: 0.301 AC: 8193 AN: 27258

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 5747 AN: 10782

East Asian (EAS) AF: 0.161 AC: 1486 AN: 9210

South Asian (SAS) AF: 0.247 AC: 14760 AN: 59720

European-Finnish (FIN) AF: 0.409 AC: 5054 AN: 12366

Middle Eastern (MID) AF: 0.373 AC: 1035 AN: 2772

European-Non Finnish (NFE) AF: 0.392 AC: 62276 AN: 158742

Other (OTH) AF: 0.366 AC: 5201 AN: 14210

GnomAD4 genome AF: 0.325 AC: 49470 AN: 152086 Hom.: 8839 Cov.: 32 AF XY: 0.323 AC XY: 24009 AN XY: 74354

African (AFR) AF: 0.193 AC: 8006 AN: 41504

American (AMR) AF: 0.349 AC: 5335 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1878 AN: 3470

East Asian (EAS) AF: 0.146 AC: 755 AN: 5178

South Asian (SAS) AF: 0.217 AC: 1047 AN: 4824

European-Finnish (FIN) AF: 0.405 AC: 4282 AN: 10570

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26962 AN: 67952

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.372 Hom.: 2063

Bravo AF: 0.316

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.36
PhyloP100		0.56
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: rs34133110; hg19: chr16-50743919; COSMIC: COSV107363623; COSMIC: COSV107363623;