rs2907749

Positions:

• chr7-30446125-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000222823.9(NOD1):​c.2453+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,592,430 control chromosomes in the GnomAD database, including 72,342 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 0.35 (9927 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62415 hom.)
• Consequence: NOD1 ENST00000222823.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.91

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD1	NM_006092.4	c.2453+16T>C		intron_variant		ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.2453+16T>C		intron_variant		1	NM_006092.4	ENSP00000222823	P1
NOD1	ENST00000434755.5	c.*163+16T>C		intron_variant, NMD_transcript_variant		2		ENSP00000416946
NOD1	ENST00000489614.5	n.1837+16T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52327 AN: 151732 Hom.: 9897 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.301 AC: 75524 AN: 251288 Hom.: 12249 AF XY: 0.293 AC XY: 39763 AN XY: 135808

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.242

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.277

GnomAD4 exome AF: 0.288 AC: 415431 AN: 1440580 Hom.: 62415 Cov.: 27 AF XY: 0.286 AC XY: 205494 AN XY: 717884

Gnomad4 AFR exome AF: 0.506

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.345 AC: 52392 AN: 151850 Hom.: 9927 Cov.: 32 AF XY: 0.338 AC XY: 25108 AN XY: 74212

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.315

Alfa AF: 0.306 Hom.: 4044

Bravo AF: 0.366

Asia WGS AF: 0.210 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0070
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs2907749; hg19: chr7-30485741; COSMIC: COSV56111455;