rs2235099

Variant names:

• chr7-30452934-G-A
• rs2235099
• NM_006092.4:c.483C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000222823.9(NOD1):​c.483C>T​(p.Asp161Asp) 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 ENST00000222823.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 19 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000222823.9. 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.483C>T	p.Asp161Asp	synonymous	Exon 6 of 14	NP_006083.1
	NOD1	NM_001354849.2		c.483C>T	p.Asp161Asp	synonymous	Exon 6 of 13	NP_001341778.1
	NOD1	NR_149002.2		n.1013C>T		non_coding_transcript_exon	Exon 6 of 15

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.483C>T	p.Asp161Asp	synonymous	Exon 6 of 14	ENSP00000222823.4
	NOD1	ENST00000434755.5	TSL:2	n.483C>T		non_coding_transcript_exon	Exon 6 of 15	ENSP00000416946.1

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

GnomAD2 exomes AF: 0.271 AC: 67827 AN: 250654 AF XY: 0.276

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 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

African (AFR) AF: 0.373 AC: 12487 AN: 33478

American (AMR) AF: 0.153 AC: 6837 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6466 AN: 26136

East Asian (EAS) AF: 0.412 AC: 16366 AN: 39700

South Asian (SAS) AF: 0.378 AC: 32614 AN: 86254

European-Finnish (FIN) AF: 0.279 AC: 14881 AN: 53256

Middle Eastern (MID) AF: 0.330 AC: 1905 AN: 5768

European-Non Finnish (NFE) AF: 0.242 AC: 268539 AN: 1111942

Other (OTH) AF: 0.269 AC: 16227 AN: 60394

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

African (AFR) AF: 0.369 AC: 15277 AN: 41434

American (AMR) AF: 0.191 AC: 2919 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1871 AN: 5140

South Asian (SAS) AF: 0.387 AC: 1865 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2919 AN: 10544

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16672 AN: 67960

Other (OTH) AF: 0.301 AC: 635 AN: 2110

Alfa AF: 0.261 Hom.: 3014

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.0
DANN	Benign	0.38
PhyloP100		1.8
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: rs2235099; hg19: chr7-30492550; COSMIC: COSV56112558; COSMIC: COSV56112558;