7-30472178-C-T

Variant names:

• chr7-30472178-C-T
• rs2529440
• NM_006092.4:c.-352+6428G>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+6428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,128 control chromosomes in the GnomAD database, including 28,169 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 0.58 (28169 hom., cov: 32)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 16 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.-352+6428G>A		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.-352+6428G>A		intron_variant	Intron 1 of 13	1	NM_006092.4	ENSP00000222823.4

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87979 AN: 152010 Hom.: 28117 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.579 AC: 88082 AN: 152128 Hom.: 28169 Cov.: 32 AF XY: 0.579 AC XY: 43096 AN XY: 74378

African (AFR) AF: 0.870 AC: 36120 AN: 41538

American (AMR) AF: 0.555 AC: 8480 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1558 AN: 3470

East Asian (EAS) AF: 0.594 AC: 3067 AN: 5162

South Asian (SAS) AF: 0.528 AC: 2545 AN: 4822

European-Finnish (FIN) AF: 0.419 AC: 4437 AN: 10590

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30043 AN: 67948

Other (OTH) AF: 0.558 AC: 1180 AN: 2116

Alfa AF: 0.483 Hom.: 6645

Bravo AF: 0.605

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.78
DANN	Benign	0.37
PhyloP100		-0.12
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: rs2529440; hg19: chr7-30511794;