rs2893375

Positions:

• chr7-30471237-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006092.4(NOD1):​c.-352+7369T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,118 control chromosomes in the GnomAD database, including 2,256 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 0.17 (2256 hom., cov: 32)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.-352+7369T>G		intron_variant		ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.-352+7369T>G		intron_variant		1	NM_006092.4	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25298 AN: 152000 Hom.: 2247 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.167 AC: 25330 AN: 152118 Hom.: 2256 Cov.: 32 AF XY: 0.170 AC XY: 12626 AN XY: 74370

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.150

Alfa AF: 0.176 Hom.: 2532

Bravo AF: 0.170

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs2893375; hg19: chr7-30510853;