16-50717487-A-G

Variant names:

• chr16-50717487-A-G
• rs748855
• NM_001370466.1:c.2549+513A>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.2549+513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,966 control chromosomes in the GnomAD database, including 8,915 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 0.33 (8915 hom., cov: 33)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 18 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2549+513A>G		intron_variant	Intron 6 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2549+513A>G		intron_variant	Intron 6 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49818 AN: 151848 Hom.: 8919 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.328 AC: 49823 AN: 151966 Hom.: 8915 Cov.: 33 AF XY: 0.326 AC XY: 24202 AN XY: 74268

African (AFR) AF: 0.203 AC: 8416 AN: 41424

American (AMR) AF: 0.348 AC: 5321 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3468

East Asian (EAS) AF: 0.145 AC: 749 AN: 5166

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4812

European-Finnish (FIN) AF: 0.412 AC: 4338 AN: 10538

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26933 AN: 67968

Other (OTH) AF: 0.335 AC: 707 AN: 2110

Alfa AF: 0.357 Hom.: 1765

Bravo AF: 0.317

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		-0.077
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: rs748855; hg19: chr16-50751398;