7-30475375-T-C

Variant names:

• chr7-30475375-T-C
• rs2256023
• NM_006092.4:c.-352+3231A>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+3231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,150 control chromosomes in the GnomAD database, including 22,408 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 (22408 hom., cov: 33)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 15 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 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+3231A>G		intron	N/A	NP_006083.1
	NOD1	NM_001354849.2		c.-352+3231A>G		intron	N/A	NP_001341778.1
	NOD1	NR_149002.2		n.179+3231A>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+3231A>G		intron	N/A	ENSP00000222823.4
	NOD1	ENST00000411552.5	TSL:1	c.-352+473A>G		intron	N/A	ENSP00000396046.1
	NOD1	ENST00000413433.5	TSL:1	c.-428+3231A>G		intron	N/A	ENSP00000399505.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79943 AN: 152032 Hom.: 22386 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.526 AC: 80013 AN: 152150 Hom.: 22408 Cov.: 33 AF XY: 0.528 AC XY: 39263 AN XY: 74384

African (AFR) AF: 0.719 AC: 29853 AN: 41492

American (AMR) AF: 0.533 AC: 8144 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3094 AN: 5190

South Asian (SAS) AF: 0.524 AC: 2525 AN: 4822

European-Finnish (FIN) AF: 0.416 AC: 4408 AN: 10594

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28716 AN: 67976

Other (OTH) AF: 0.513 AC: 1084 AN: 2112

Alfa AF: 0.467 Hom.: 23251

Bravo AF: 0.546

Asia WGS AF: 0.543 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		-1.2
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: rs2256023; hg19: chr7-30514991;