NM_006092.4:c.-351-304A>G

Variant names:

• chr7-30460345-T-C
• rs3823773
• NM_006092.4:c.-351-304A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 8 publications found

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]

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	NM_006092.4	MANE Select	c.-351-304A>G		intron	N/A	NP_006083.1
	NOD1	NM_001354849.2		c.-351-304A>G		intron	N/A	NP_001341778.1
	NOD1	NR_149002.2		n.180-304A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.-351-304A>G		intron	N/A	ENSP00000222823.4
	NOD1	ENST00000411552.5	TSL:1	c.-351-304A>G		intron	N/A	ENSP00000396046.1
	NOD1	ENST00000413433.5	TSL:1	c.-351-304A>G		intron	N/A	ENSP00000399505.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12143 AN: 152124 Hom.: 608 Cov.: 33

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.: 30 AF XY: 0.108 AC XY: 41387 AN XY: 384714

African (AFR) AF: 0.0241 AC: 381 AN: 15786

American (AMR) AF: 0.0620 AC: 61 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: 28 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

GnomAD4 genome AF: 0.0799 AC: 12166 AN: 152242 Hom.: 609 Cov.: 33 AF XY: 0.0780 AC XY: 5804 AN XY: 74432

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7324 AN: 68006

Other (OTH) AF: 0.110 AC: 233 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.76
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3823773; hg19: chr7-30499961;