Variant rs34133110 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001370466.1(NOD2):c.566-550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 455,762 control chromosomes in the GnomAD database, including 28,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 8839 hom., cov: 32)

Exomes 𝑓: 0.35 ( 19802 hom. )

Consequence

NOD2
NM_001370466.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.563

Variant links:

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 links:

NOD2 (HGNC:):

NOD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-50710008-C-T is Benign according to our data. Variant chr16-50710008-C-T is described in ClinVar as [Benign]. Clinvar id is 2688030.Status of the report is criteria_provided_single_submitter, 1 stars.

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 linkuse as main transcript	c.566-550C>T		intron_variant		ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.566-550C>T		intron_variant			NM_001370466.1	ENSP00000495993.1		Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49467

AN:

151966

Hom.:

8843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.345

GnomAD3 exomes

AF:

0.326

AC:

41720

AN:

128010

Hom.:

7554

AF XY:

0.325

AC XY:

22750

AN XY:

70102

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.532

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.347

AC:

105379

AN:

303676

Hom.:

19802

Cov.:

AF XY:

0.339

AC XY:

58702

AN XY:

172938

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.533

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.325

AC:

49470

AN:

152086

Hom.:

8839

Cov.:

AF XY:

0.323

AC XY:

24009

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.372

Hom.:

2063

Bravo

AF:

0.316

Asia WGS

AF:

0.188

AC:

652

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over