rs2075819

Positions:

• chr7-30455006-T-C

Variant summary

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

The NM_006092.4(NOD1):​c.376+131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 851,424 control chromosomes in the GnomAD database, including 40,280 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 0.33 (9241 hom., cov: 32)
  • Exomes 𝑓: 0.29 (31039 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.376+131A>G		intron_variant		ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.376+131A>G		intron_variant		1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.376+131A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50496 AN: 151902 Hom.: 9233 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.288 AC: 201666 AN: 699404 Hom.: 31039 AF XY: 0.293 AC XY: 105763 AN XY: 361164

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.332 AC: 50534 AN: 152020 Hom.: 9241 Cov.: 32 AF XY: 0.334 AC XY: 24815 AN XY: 74294

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.350

Alfa AF: 0.283 Hom.: 10579

Bravo AF: 0.334

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.71

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: rs2075819; hg19: chr7-30494622; COSMIC: COSV56112252; COSMIC: COSV56112252;