16-50725636-A-T

Variant names:

• chr16-50725636-A-T
• rs1077861
• NM_001370466.1:c.2885+64A>T

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.2885+64A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,297,068 control chromosomes in the GnomAD database, including 240,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (22312 hom., cov: 31)
  • Exomes 𝑓: 0.60 (217836 hom.)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44
• Publications: 32 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=-0.94).
• BP6: Variant 16-50725636-A-T is Benign according to our data. Variant chr16-50725636-A-T is described in ClinVar as Benign. ClinVar VariationId is 2628170.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	NM_001370466.1	MANE Select	c.2885+64A>T		intron	N/A	NP_001357395.1
	NOD2	NM_022162.3		c.2966+64A>T		intron	N/A	NP_071445.1
	NOD2	NM_001293557.2		c.2885+64A>T		intron	N/A	NP_001280486.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	ENST00000647318.2	MANE Select	c.2885+64A>T		intron	N/A	ENSP00000495993.1
	NOD2	ENST00000300589.6	TSL:1	c.2966+64A>T		intron	N/A	ENSP00000300589.2
	NOD2	ENST00000951248.1		c.2885+64A>T		intron	N/A	ENSP00000621307.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77301 AN: 151924 Hom.: 22315 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.602 AC: 688886 AN: 1145026 Hom.: 217836 AF XY: 0.597 AC XY: 349311 AN XY: 584652

African (AFR) AF: 0.272 AC: 7359 AN: 27088

American (AMR) AF: 0.417 AC: 18347 AN: 43994

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 18564 AN: 23990

East Asian (EAS) AF: 0.177 AC: 6704 AN: 37908

South Asian (SAS) AF: 0.392 AC: 31171 AN: 79492

European-Finnish (FIN) AF: 0.568 AC: 29772 AN: 52458

Middle Eastern (MID) AF: 0.607 AC: 2963 AN: 4880

European-Non Finnish (NFE) AF: 0.661 AC: 545421 AN: 825382

Other (OTH) AF: 0.574 AC: 28585 AN: 49834

GnomAD4 genome AF: 0.509 AC: 77318 AN: 152042 Hom.: 22312 Cov.: 31 AF XY: 0.501 AC XY: 37239 AN XY: 74346

African (AFR) AF: 0.275 AC: 11424 AN: 41470

American (AMR) AF: 0.511 AC: 7803 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2646 AN: 3462

East Asian (EAS) AF: 0.152 AC: 787 AN: 5172

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5989 AN: 10580

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44949 AN: 67950

Other (OTH) AF: 0.543 AC: 1149 AN: 2116

Alfa AF: 0.569 Hom.: 3327

Bravo AF: 0.492

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.012
DANN	Benign	0.43
PhyloP100		-2.4
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: rs1077861; hg19: chr16-50759547; COSMIC: COSV56051513; COSMIC: COSV56051513;