16-50697256-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_022162.3(NOD2):ā€‹c.13G>Cā€‹(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,558,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00035 ( 0 hom., cov: 32)
Exomes š‘“: 0.000047 ( 0 hom. )

Consequence

NOD2
NM_022162.3 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.172
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009373516).
BP6
Variant 16-50697256-G-C is Benign according to our data. Variant chr16-50697256-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 732125.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000348 (53/152192) while in subpopulation AFR AF= 0.00121 (50/41450). AF 95% confidence interval is 0.00094. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOD2NM_001370466.1 linkc.-8-2232G>C intron_variant ENST00000647318.2 NP_001357395.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOD2ENST00000647318.2 linkc.-8-2232G>C intron_variant NM_001370466.1 ENSP00000495993.1 Q9HC29-2

Frequencies

GnomAD3 genomes
AF:
0.000348
AC:
53
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000119
AC:
20
AN:
167788
Hom.:
0
AF XY:
0.0000451
AC XY:
4
AN XY:
88622
show subpopulations
Gnomad AFR exome
AF:
0.00206
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000469
AC:
66
AN:
1405840
Hom.:
0
Cov.:
31
AF XY:
0.0000375
AC XY:
26
AN XY:
694102
show subpopulations
Gnomad4 AFR exome
AF:
0.00178
Gnomad4 AMR exome
AF:
0.0000545
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.0000858
GnomAD4 genome
AF:
0.000348
AC:
53
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00121
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000451
Hom.:
0
Bravo
AF:
0.000408
ESP6500AA
AF:
0.00160
AC:
7
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000436
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Regional enteritis;C5201146:Blau syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 07, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
1.2
DANN
Benign
0.78
DEOGEN2
Benign
0.069
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.075
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.0094
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.30
N
REVEL
Benign
0.12
Sift
Pathogenic
0.0
D
Polyphen
0.089
B
Vest4
0.087
MVP
0.66
MPC
0.22
ClinPred
0.10
T
GERP RS
-0.61
Varity_R
0.099
gMVP
0.058

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.

Other links and lift over

dbSNP: rs140977130; hg19: chr16-50731167; API