7-30464322-G-A

Variant names:

• chr7-30464322-G-A
• rs4363092
• NM_006092.4:c.-351-4281C>T

Variant summary

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

The NM_006092.4(NOD1):​c.-351-4281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,204 control chromosomes in the GnomAD database, including 2,075 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 0.15 (2075 hom., cov: 33)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.-351-4281C>T		intron_variant	Intron 1 of 13	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.-351-4281C>T		intron_variant	Intron 1 of 13	1	NM_006092.4	ENSP00000222823.4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23506 AN: 152086 Hom.: 2076 Cov.: 33

Gnomad AFR AF: 0.0716

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.154 AC: 23502 AN: 152204 Hom.: 2075 Cov.: 33 AF XY: 0.157 AC XY: 11714 AN XY: 74410

African (AFR) AF: 0.0717 AC: 2978 AN: 41560

American (AMR) AF: 0.228 AC: 3481 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 682 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5168

South Asian (SAS) AF: 0.182 AC: 879 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1744 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11903 AN: 67996

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.155 Hom.: 270

Bravo AF: 0.156

Asia WGS AF: 0.158 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.87
DANN	Benign	0.41
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4363092; hg19: chr7-30503938;