rs4720004

Positions:

• chr7-30472603-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.-352+6003A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,242 control chromosomes in the GnomAD database, including 1,822 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 0.14 (1822 hom., cov: 33)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD1	NM_006092.4	c.-352+6003A>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.-352+6003A>G		intron_variant		1	NM_006092.4	ENSP00000222823	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21790 AN: 152124 Hom.: 1823 Cov.: 33

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.143 AC: 21786 AN: 152242 Hom.: 1822 Cov.: 33 AF XY: 0.147 AC XY: 10977 AN XY: 74444

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.135

Alfa AF: 0.159 Hom.: 355

Bravo AF: 0.145

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.27

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: rs4720004; hg19: chr7-30512219;