7-30469376-C-T

Variant names:

• chr7-30469376-C-T
• rs4720003
• NM_006092.4:c.-352+9230G>A

Variant summary

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

The NM_006092.4(NOD1):​c.-352+9230G>A 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 152,098 control chromosomes in the GnomAD database, including 2,265 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 (2265 hom., cov: 32)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.16
• Publications: 7 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]

ENSG00000302674 (HGNC:):

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 = 0.226 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	NM_006092.4	MANE Select	c.-352+9230G>A		intron	N/A	NP_006083.1
	NOD1	NM_001354849.2		c.-352+9230G>A		intron	N/A	NP_001341778.1
	NOD1	NR_149002.2		n.179+9230G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.-352+9230G>A		intron	N/A	ENSP00000222823.4
	NOD1	ENST00000411552.5	TSL:1	c.-352+6472G>A		intron	N/A	ENSP00000396046.1
	NOD1	ENST00000413433.5	TSL:1	c.-427-5315G>A		intron	N/A	ENSP00000399505.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25322 AN: 151980 Hom.: 2256 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.167 AC: 25354 AN: 152098 Hom.: 2265 Cov.: 32 AF XY: 0.170 AC XY: 12638 AN XY: 74358

African (AFR) AF: 0.113 AC: 4694 AN: 41500

American (AMR) AF: 0.233 AC: 3554 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5152

South Asian (SAS) AF: 0.183 AC: 883 AN: 4816

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10598

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11927 AN: 67968

Other (OTH) AF: 0.149 AC: 315 AN: 2110

Alfa AF: 0.0589 Hom.: 72

Bravo AF: 0.170

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.69
PhyloP100		-5.2
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: rs4720003; hg19: chr7-30508992;