rs2235099

chr7-30452934-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006092.4(NOD1):c.483C>T(p.Asp161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,613,624 control chromosomes in the GnomAD database, including 57,135 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 0.28 (6561 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50574 hom.)
• Consequence: NOD1 NM_006092.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.483C>T	p.Asp161=	synonymous_variant	6/14	ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.483C>T	p.Asp161=	synonymous_variant	6/14	1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.483C>T	p.Asp161=	synonymous_variant, NMD_transcript_variant	6/15	2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43152 AN: 151854 Hom.: 6555 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.271 AC: 67827 AN: 250654 Hom.: 9927 AF XY: 0.276 AC XY: 37460 AN XY: 135512

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.350

Gnomad SAS exome AF: 0.379

Gnomad FIN exome AF: 0.280

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.257 AC: 376322 AN: 1461652 Hom.: 50574 Cov.: 38 AF XY: 0.261 AC XY: 190041 AN XY: 727126

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.412

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.284 AC: 43182 AN: 151972 Hom.: 6561 Cov.: 32 AF XY: 0.286 AC XY: 21271 AN XY: 74262

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.301

Alfa AF: 0.260 Hom.: 2948

Bravo AF: 0.281

Asia WGS AF: 0.370 AC: 1282 AN: 3478

EpiCase AF: 0.253

EpiControl AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	8.0
Dann	Benign	0.38

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: rs2235099; hg19: chr7-30492550; COSMIC: COSV56112558; COSMIC: COSV56112558;