7-30473155-A-C

Variant names:

• chr7-30473155-A-C
• rs2709800
• NM_006092.4:c.-352+5451T>G

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+5451T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,994 control chromosomes in the GnomAD database, including 22,844 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 0.53 (22844 hom., cov: 32)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	NM_006092.4	MANE Select	c.-352+5451T>G		intron	N/A	NP_006083.1
	NOD1	NM_001354849.2		c.-352+5451T>G		intron	N/A	NP_001341778.1
	NOD1	NR_149002.2		n.179+5451T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.-352+5451T>G		intron	N/A	ENSP00000222823.4
	NOD1	ENST00000411552.5	TSL:1	c.-352+2693T>G		intron	N/A	ENSP00000396046.1
	NOD1	ENST00000413433.5	TSL:1	c.-428+5451T>G		intron	N/A	ENSP00000399505.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80576 AN: 151876 Hom.: 22814 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.531 AC: 80656 AN: 151994 Hom.: 22844 Cov.: 32 AF XY: 0.533 AC XY: 39583 AN XY: 74290

African (AFR) AF: 0.735 AC: 30477 AN: 41446

American (AMR) AF: 0.534 AC: 8163 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1557 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3079 AN: 5172

South Asian (SAS) AF: 0.522 AC: 2509 AN: 4810

European-Finnish (FIN) AF: 0.425 AC: 4481 AN: 10542

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28644 AN: 67948

Other (OTH) AF: 0.520 AC: 1097 AN: 2108

Alfa AF: 0.467 Hom.: 52312

Bravo AF: 0.551

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.54
PhyloP100		-0.090
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: rs2709800; hg19: chr7-30512771;