chr16-50707551-A-C

Variant names:

• chr16-50707551-A-C
• rs17312836
• NM_001370466.1:c.460-304A>C

Variant summary

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

The NM_001370466.1(NOD2):​c.460-304A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,068 control chromosomes in the GnomAD database, including 9,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9148 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.406
• Publications: 17 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=-0.9).
• BP6: Variant 16-50707551-A-C is Benign according to our data. Variant chr16-50707551-A-C is described in ClinVar as Benign. ClinVar VariationId is 1250150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370466.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	NM_001370466.1	MANE Select	c.460-304A>C		intron	N/A	NP_001357395.1
	NOD2	NM_022162.3		c.541-304A>C		intron	N/A	NP_071445.1
	NOD2	NM_001293557.2		c.460-304A>C		intron	N/A	NP_001280486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	ENST00000647318.2	MANE Select	c.460-304A>C		intron	N/A	ENSP00000495993.1
	NOD2	ENST00000300589.6	TSL:1	c.541-304A>C		intron	N/A	ENSP00000300589.2
	NOD2	ENST00000527070.5	TSL:1	c.460-304A>C		intron	N/A	ENSP00000435149.2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50480 AN: 151950 Hom.: 9152 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.332 AC: 50484 AN: 152068 Hom.: 9148 Cov.: 32 AF XY: 0.330 AC XY: 24532 AN XY: 74344

African (AFR) AF: 0.205 AC: 8520 AN: 41478

American (AMR) AF: 0.351 AC: 5372 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3468

East Asian (EAS) AF: 0.147 AC: 761 AN: 5180

South Asian (SAS) AF: 0.217 AC: 1050 AN: 4832

European-Finnish (FIN) AF: 0.424 AC: 4476 AN: 10550

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

European-Non Finnish (NFE) AF: 0.400 AC: 27212 AN: 67956

Other (OTH) AF: 0.344 AC: 728 AN: 2114

Alfa AF: 0.351 Hom.: 2073

Bravo AF: 0.322

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.50
PhyloP100		-0.41
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: rs17312836; hg19: chr16-50741462;