7-30433407-C-T

Variant names:

• chr7-30433407-C-T
• rs2907748
• NM_006092.4:c.2622-228G>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.2622-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 539,704 control chromosomes in the GnomAD database, including 14,773 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 0.20 (3623 hom., cov: 31)
  • Exomes 𝑓: 0.24 (11150 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 21 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 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.2622-228G>A		intron	N/A	NP_006083.1	Q9Y239-1
	NOD1	NM_001354849.2		c.2538-228G>A		intron	N/A	NP_001341778.1	Q9Y239-3
	NOD1	NR_149002.2		n.3202-228G>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.2622-228G>A		intron	N/A	ENSP00000222823.4	Q9Y239-1
	NOD1	ENST00000855556.1		c.2622-228G>A		intron	N/A	ENSP00000525615.1
	NOD1	ENST00000855558.1		c.2622-228G>A		intron	N/A	ENSP00000525617.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30807 AN: 151684 Hom.: 3619 Cov.: 31

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.236 AC: 91482 AN: 387902 Hom.: 11150 Cov.: 2 AF XY: 0.237 AC XY: 48464 AN XY: 204284

African (AFR) AF: 0.0828 AC: 943 AN: 11386

American (AMR) AF: 0.306 AC: 3906 AN: 12784

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 3046 AN: 12216

East Asian (EAS) AF: 0.240 AC: 6729 AN: 28016

South Asian (SAS) AF: 0.231 AC: 8160 AN: 35262

European-Finnish (FIN) AF: 0.172 AC: 4583 AN: 26672

Middle Eastern (MID) AF: 0.189 AC: 326 AN: 1728

European-Non Finnish (NFE) AF: 0.247 AC: 58651 AN: 237248

Other (OTH) AF: 0.227 AC: 5138 AN: 22590

GnomAD4 genome AF: 0.203 AC: 30813 AN: 151802 Hom.: 3623 Cov.: 31 AF XY: 0.201 AC XY: 14917 AN XY: 74152

African (AFR) AF: 0.0884 AC: 3664 AN: 41454

American (AMR) AF: 0.283 AC: 4297 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1283 AN: 5128

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4818

European-Finnish (FIN) AF: 0.181 AC: 1897 AN: 10488

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16919 AN: 67928

Other (OTH) AF: 0.201 AC: 423 AN: 2106

Alfa AF: 0.236 Hom.: 5772

Bravo AF: 0.208

Asia WGS AF: 0.175 AC: 611 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.33
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: rs2907748; hg19: chr7-30473023;