rs34133110

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

Blau syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Illumina, ClinGen, Labcorp Genetics (formerly Invitae)
inflammatory bowel disease 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NOD2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001370466.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOD2	NM_001370466.1	MANE Select	c.566-550C>T	intron	N/A	NP_001357395.1	Q9HC29-2
NOD2	NM_022162.3		c.647-550C>T	intron	N/A	NP_071445.1	Q9HC29-1
NOD2	NM_001293557.2		c.566-550C>T	intron	N/A	NP_001280486.1	Q9HC29-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOD2	ENST00000647318.2	MANE Select	c.566-550C>T	intron	N/A	ENSP00000495993.1	Q9HC29-2
NOD2	ENST00000300589.6	TSL:1	c.647-550C>T	intron	N/A	ENSP00000300589.2	Q9HC29-1
NOD2	ENST00000527070.5	TSL:1	c.566-550C>T	intron	N/A	ENSP00000435149.2	E9PLF7

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

GnomAD2 exomes

AF:

0.326

AC:

41720

AN:

128010

AF XY:

0.325

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 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

African (AFR)

AF:

0.189

AC:

1627

AN:

8616

American (AMR)

AF:

0.301

AC:

8193

AN:

27258

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

5747

AN:

10782

East Asian (EAS)

AF:

0.161

AC:

1486

AN:

9210

South Asian (SAS)

AF:

0.247

AC:

14760

AN:

59720

European-Finnish (FIN)

AF:

0.409

AC:

5054

AN:

12366

Middle Eastern (MID)

AF:

0.373

AC:

1035

AN:

2772

European-Non Finnish (NFE)

AF:

0.392

AC:

62276

AN:

158742

Other (OTH)

AF:

0.366

AC:

5201

AN:

14210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

3799

7598

11397

15196

18995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.325

AC:

49470

AN:

152086

Hom.:

8839

Cov.:

AF XY:

0.323

AC XY:

24009

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.193

AC:

8006

AN:

41504

American (AMR)

AF:

0.349

AC:

5335

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1878

AN:

3470

East Asian (EAS)

AF:

0.146

AC:

755

AN:

5178

South Asian (SAS)

AF:

0.217

AC:

1047

AN:

4824

European-Finnish (FIN)

AF:

0.405

AC:

4282

AN:

10570

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.397

AC:

26962

AN:

67952

Other (OTH)

AF:

0.341

AC:

718

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1616

3233

4849

6466

8082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.372

Hom.:

2063

Bravo

AF:

0.316

Asia WGS

AF:

0.188

AC:

652

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.8

(source)

DANN

Benign

0.36

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over