dbSNP rs2906766: NOD1:c.-269A>G (chr7-30459959-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.-269A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,716 control chromosomes in the GnomAD database, including 11,924 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 0.38 ( 11884 hom., cov: 33)

Exomes 𝑓: 0.34 ( 40 hom. )

Consequence

NOD1
NM_006092.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.902

Publications

19 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4 link	c.-269A>G		5_prime_UTR_variant	Exon 2 of 14	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.-269A>G		5_prime_UTR_variant	Exon 2 of 14	1	NM_006092.4	ENSP00000222823.4		Q9Y239-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57750

AN:

151946

Hom.:

11877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.339

AC:

221

AN:

652

Hom.:

Cov.:

AF XY:

0.353

AC XY:

125

AN XY:

354

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.345

AC:

147

AN:

426

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.308

AC:

AN:

198

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.380

AC:

57791

AN:

152064

Hom.:

11884

Cov.:

AF XY:

0.380

AC XY:

28266

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.539

AC:

22339

AN:

41460

American (AMR)

AF:

0.316

AC:

4829

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

939

AN:

3462

East Asian (EAS)

AF:

0.371

AC:

1919

AN:

5170

South Asian (SAS)

AF:

0.376

AC:

1810

AN:

4820

European-Finnish (FIN)

AF:

0.353

AC:

3733

AN:

10566

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21096

AN:

67992

Other (OTH)

AF:

0.380

AC:

802

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1817

3634

5450

7267

9084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.330

Hom.:

14610

Bravo

AF:

0.387

Asia WGS

AF:

0.390

AC:

1352

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.30

PhyloP100

-0.90

Mutation Taster

=296/4

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

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