rs11647841

Variant names:

• chr16-50709420-G-A
• rs11647841
• NM_001370466.1:c.566-1138G>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.566-1138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,056 control chromosomes in the GnomAD database, including 8,826 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 (8826 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 21 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=-0.86).
• 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.566-1138G>A		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.566-1138G>A		intron_variant	Intron 3 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49432 AN: 151938 Hom.: 8830 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: 0.144

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.325 AC: 49435 AN: 152056 Hom.: 8826 Cov.: 32 AF XY: 0.323 AC XY: 23980 AN XY: 74320

African (AFR) AF: 0.193 AC: 7997 AN: 41470

American (AMR) AF: 0.349 AC: 5335 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3468

East Asian (EAS) AF: 0.144 AC: 746 AN: 5182

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4820

European-Finnish (FIN) AF: 0.404 AC: 4268 AN: 10560

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

European-Non Finnish (NFE) AF: 0.397 AC: 26972 AN: 67966

Other (OTH) AF: 0.339 AC: 717 AN: 2114

Alfa AF: 0.379 Hom.: 41911

Bravo AF: 0.316

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.70
DANN	Benign	0.49
PhyloP100		-0.66
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: rs11647841; hg19: chr16-50743331;