rs3823773

Positions:

• chr7-30460345-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NOD1	NM_006092.4	c.-351-304A>G		intron_variant		ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.-351-304A>G		intron_variant		1	NM_006092.4	ENSP00000222823	P1

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

Gnomad4 AFR exome AF: 0.0241

Gnomad4 AMR exome AF: 0.0620

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.110

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

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.110

Alfa AF: 0.104 Hom.: 853

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
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs3823773; hg19: chr7-30499961;