16-50696236-C-T

Position:

• chr16-50696236-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001370466.1(NOD2):​c.-9+2574C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 152,430 control chromosomes in the GnomAD database, including 3 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 0.0039 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (0 hom.)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00391 (595/152298) while in subpopulation AFR AF= 0.00763 (317/41552). AF 95% confidence interval is 0.00694. There are 3 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.-9+2574C>T		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+2574C>T		intron_variant			NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152180 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00758 AC: 1 AN: 132 Hom.: 0 AF XY: 0.0100 AC XY: 1 AN XY: 100

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00980

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152298 Hom.: 3 Cov.: 33 AF XY: 0.00373 AC XY: 278 AN XY: 74474

Gnomad4 AFR AF: 0.00763

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00423

Asia WGS AF: 0.00144 AC: 5 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	5.1
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743260; hg19: chr16-50730147;