NM_001370466.1:c.460-2661G>A

Variant names:

• chr16-50705194-G-A
• rs13339578
• NM_001370466.1:c.460-2661G>A

Variant summary

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

The NM_001370466.1(NOD2):​c.460-2661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,024 control chromosomes in the GnomAD database, including 30,746 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30746 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.460-2661G>A		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.460-2661G>A		intron_variant	Intron 2 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95024 AN: 151908 Hom.: 30723 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.626 AC: 95101 AN: 152024 Hom.: 30746 Cov.: 32 AF XY: 0.616 AC XY: 45793 AN XY: 74316

African (AFR) AF: 0.604 AC: 25058 AN: 41460

American (AMR) AF: 0.580 AC: 8863 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2708 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1016 AN: 5176

South Asian (SAS) AF: 0.354 AC: 1703 AN: 4816

European-Finnish (FIN) AF: 0.621 AC: 6535 AN: 10530

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 46997 AN: 67962

Other (OTH) AF: 0.636 AC: 1345 AN: 2114

Alfa AF: 0.620 Hom.: 5899

Bravo AF: 0.623

Asia WGS AF: 0.303 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.36
PhyloP100		-0.87
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: rs13339578; hg19: chr16-50739105;