Genetic Variant NM_006092.4:c.2360C>G (chr7-30446976-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006092.4(NOD1):c.2360C>G(p.Thr787Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T787M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

NOD1
NM_006092.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0500

Publications

5 publications found

Variant links:

Genes affected

NOD1 (HGNC:16390): (nucleotide binding oligomerization domain containing 1) This gene encodes a member of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins. The encoded protein plays a role in innate immunity by acting as a pattern-recognition receptor (PRR) that binds bacterial peptidoglycans and initiates inflammation. This protein has also been implicated in the immune response to viral and parasitic infection. Major structural features of this protein include an N-terminal caspase recruitment domain (CARD), a centrally located nucleotide-binding domain (NBD), and 10 tandem leucine-rich repeats (LRRs) in its C terminus. The CARD is involved in apoptotic signaling, LRRs participate in protein-protein interactions, and mutations in the NBD may affect the process of oligomerization and subsequent function of the LRR domain. Mutations in this gene are associated with asthma, inflammatory bowel disease, Behcet disease and sarcoidosis in human patients. [provided by RefSeq, Aug 2017]

NOD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058070213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006092.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOD1	NM_006092.4	MANE Select	c.2360C>G	p.Thr787Arg	missense	Exon 8 of 14	NP_006083.1	Q9Y239-1
NOD1	NM_001354849.2		c.2360C>G	p.Thr787Arg	missense	Exon 8 of 13	NP_001341778.1	Q9Y239-3
NOD1	NR_149002.2		n.2949+39C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOD1	ENST00000222823.9	TSL:1 MANE Select	c.2360C>G	p.Thr787Arg	missense	Exon 8 of 14	ENSP00000222823.4	Q9Y239-1
NOD1	ENST00000855556.1		c.2360C>G	p.Thr787Arg	missense	Exon 9 of 15	ENSP00000525615.1
NOD1	ENST00000855558.1		c.2360C>G	p.Thr787Arg	missense	Exon 9 of 15	ENSP00000525617.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

2.0

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.050

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.70

M_CAP

Benign

0.022

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.64

PhyloP100

0.050

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

REVEL

Benign

0.043

Sift

Benign

0.76

Sift4G

Benign

0.59

Polyphen

0.018

Vest4

0.35

MutPred

0.33

Gain of MoRF binding (P = 0.0129)

MVP

0.43

MPC

0.37

ClinPred

0.022

GERP RS

1.8

Varity_R

0.051

gMVP

0.38

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: -9

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over