rs2075822

chr7-30451144-A-Gchr7-30451144-A-T

Variant summary

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

The NM_006092.4(NOD1):c.2201+72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,512,272 control chromosomes in the GnomAD database, including 37,186 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 0.19 (3034 hom., cov: 32)
  • Exomes 𝑓: 0.22 (34152 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.2201+72T>C		intron_variant		ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.2201+72T>C		intron_variant		1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.2201+72T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29132 AN: 152028 Hom.: 3034 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.221 AC: 300694 AN: 1360126 Hom.: 34152 AF XY: 0.220 AC XY: 147719 AN XY: 671836

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.191 AC: 29129 AN: 152146 Hom.: 3034 Cov.: 32 AF XY: 0.192 AC XY: 14277 AN XY: 74396

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.181

Alfa AF: 0.211 Hom.: 883

Bravo AF: 0.196

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.30
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: rs2075822; hg19: chr7-30490760; COSMIC: COSV56115628; COSMIC: COSV56115628;