Genetic Variant NM_006092.4:c.2706-1796C>G (chr7-30431253-G-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.2706-1796C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,074 control chromosomes in the GnomAD database, including 8,870 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 0.33 ( 8870 hom., cov: 33)

Consequence

NOD1
NM_006092.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.558

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
NOD1	NM_006092.4	MANE Select	c.2706-1796C>G	intron	N/A	NP_006083.1	Q9Y239-1
NOD1	NM_001354849.2		c.2622-1796C>G	intron	N/A	NP_001341778.1	Q9Y239-3
NOD1	NR_149002.2		n.3286-1796C>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOD1	ENST00000222823.9	TSL:1 MANE Select	c.2706-1796C>G	intron	N/A	ENSP00000222823.4	Q9Y239-1
NOD1	ENST00000855556.1		c.2706-1796C>G	intron	N/A	ENSP00000525615.1
NOD1	ENST00000855558.1		c.2706-1796C>G	intron	N/A	ENSP00000525617.1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50622

AN:

151954

Hom.:

8843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.333

AC:

50686

AN:

152074

Hom.:

8870

Cov.:

AF XY:

0.328

AC XY:

24355

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.439

AC:

18206

AN:

41460

American (AMR)

AF:

0.351

AC:

5360

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1011

AN:

3466

East Asian (EAS)

AF:

0.261

AC:

1351

AN:

5180

South Asian (SAS)

AF:

0.256

AC:

1236

AN:

4826

European-Finnish (FIN)

AF:

0.213

AC:

2253

AN:

10580

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20077

AN:

67964

Other (OTH)

AF:

0.309

AC:

649

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1724

3447

5171

6894

8618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.303

Hom.:

877

Bravo

AF:

0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.33

(source)

DANN

Benign

0.56

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over