rs13339578

Positions:

• chr16-50705194-G-A
• chr16-50705194-G-C
• chr16-50705194-G-T

Variant summary

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

The NM_001370466.1(NOD2):​c.460-2661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,024 control chromosomes in the GnomAD database, including 30,746 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 0.63 (30746 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD2	NM_001370466.1	c.460-2661G>A		intron_variant		ENST00000647318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD2	ENST00000647318.2	c.460-2661G>A		intron_variant			NM_001370466.1	P1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95024 AN: 151908 Hom.: 30723 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.626 AC: 95101 AN: 152024 Hom.: 30746 Cov.: 32 AF XY: 0.616 AC XY: 45793 AN XY: 74316

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.636

Alfa AF: 0.620 Hom.: 5002

Bravo AF: 0.623

Asia WGS AF: 0.303 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs13339578; hg19: chr16-50739105;