chr16-50696535-G-A

Position:

• chr16-50696535-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370466.1(NOD2):​c.-9+2873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,362 control chromosomes in the GnomAD database, including 10,668 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 0.37 (10660 hom., cov: 33)
  • Exomes 𝑓: 0.24 (8 hom.)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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/exons	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.-9+2873G>A		intron_variant		ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.-9+2873G>A		intron_variant			NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55762 AN: 151974 Hom.: 10662 Cov.: 33

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.243 AC: 65 AN: 268 Hom.: 8 AF XY: 0.285 AC XY: 49 AN XY: 172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0833

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.367 AC: 55773 AN: 152094 Hom.: 10660 Cov.: 33 AF XY: 0.362 AC XY: 26917 AN XY: 74342

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.361

Alfa AF: 0.390 Hom.: 11416

Bravo AF: 0.362

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4785224; hg19: chr16-50730446;