dbSNP rs3823773: NOD1:c.-351-304A>G (chr7-30460345-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006092.4(NOD1):c.-351-304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 985,352 control chromosomes in the GnomAD database, including 5,571 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 0.080 ( 609 hom., cov: 33)

Exomes 𝑓: 0.11 ( 4962 hom. )

Consequence

NOD1
NM_006092.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.375

Publications

8 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4 link	c.-351-304A>G		intron_variant	Intron 1 of 13	ENST00000222823.9	NP_006083.1	Q9Y239-1A0A024RA73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9 link	c.-351-304A>G		intron_variant	Intron 1 of 13	1	NM_006092.4	ENSP00000222823.4		Q9Y239-1

Frequencies

GnomAD3 genomes

AF:

0.0798

AC:

12143

AN:

152124

Hom.:

608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0681

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0593

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.108

AC:

89694

AN:

833110

Hom.:

4962

Cov.:

AF XY:

0.108

AC XY:

41387

AN XY:

384714

show subpopulations

African (AFR)

AF:

0.0241

AC:

381

AN:

15786

American (AMR)

AF:

0.0620

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

539

AN:

5152

East Asian (EAS)

AF:

0.119

AC:

432

AN:

3630

South Asian (SAS)

AF:

0.121

AC:

1986

AN:

16460

European-Finnish (FIN)

AF:

0.101

AC:

AN:

276

Middle Eastern (MID)

AF:

0.160

AC:

259

AN:

1620

European-Non Finnish (NFE)

AF:

0.109

AC:

83018

AN:

761904

Other (OTH)

AF:

0.110

AC:

2990

AN:

27298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

5062

10123

15185

20246

25308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4146

8292

12438

16584

20730

<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:

0.0799

AC:

12166

AN:

152242

Hom.:

609

Cov.:

AF XY:

0.0780

AC XY:

5804

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0291

AC:

1210

AN:

41566

American (AMR)

AF:

0.0686

AC:

1050

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

348

AN:

3470

East Asian (EAS)

AF:

0.132

AC:

679

AN:

5160

South Asian (SAS)

AF:

0.129

AC:

619

AN:

4816

European-Finnish (FIN)

AF:

0.0593

AC:

629

AN:

10606

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7324

AN:

68006

Other (OTH)

AF:

0.110

AC:

233

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

564

1128

1691

2255

2819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.101

Hom.:

1204

Bravo

AF:

0.0799

Asia WGS

AF:

0.138

AC:

480

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

(source)

DANN

Benign

0.76

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over