rs8057341

Variant names:

• chr16-50704069-A-G
• rs8057341
• NM_001370466.1:c.460-3786A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370466.1(NOD2):​c.460-3786A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,158 control chromosomes in the GnomAD database, including 35,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (no stars).

• Frequency: Genomes: 𝑓 0.67 (35727 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: confers sensitivity no assertion criteria provided O:1
• Conservation: PhyloP100: -0.941
• Publications: 43 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.460-3786A>G		intron_variant	Intron 2 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.460-3786A>G		intron_variant	Intron 2 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102307 AN: 152040 Hom.: 35683 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.673 AC: 102407 AN: 152158 Hom.: 35727 Cov.: 32 AF XY: 0.662 AC XY: 49212 AN XY: 74392

African (AFR) AF: 0.766 AC: 31808 AN: 41516

American (AMR) AF: 0.593 AC: 9069 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2724 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5178

South Asian (SAS) AF: 0.356 AC: 1720 AN: 4826

European-Finnish (FIN) AF: 0.622 AC: 6586 AN: 10592

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47190 AN: 67978

Other (OTH) AF: 0.665 AC: 1401 AN: 2108

Alfa AF: 0.683 Hom.: 73886

Bravo AF: 0.677

Asia WGS AF: 0.314 AC: 1096 AN: 3478

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Jun 10, 2022

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

Significance: confers sensitivity

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.26
PhyloP100		-0.94
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: rs8057341; hg19: chr16-50737980;