chr7-30459959-T-C

Position:

• chr7-30459959-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.-269A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,716 control chromosomes in the GnomAD database, including 11,924 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 0.38 (11884 hom., cov: 33)
  • Exomes 𝑓: 0.34 (40 hom.)
• Consequence: NOD1 NM_006092.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902

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 = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD1	NM_006092.4	c.-269A>G		5_prime_UTR_variant	2/14	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.-269A>G		5_prime_UTR_variant	2/14	1	NM_006092.4	ENSP00000222823	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57750 AN: 151946 Hom.: 11877 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.339 AC: 221 AN: 652 Hom.: 40 Cov.: 0 AF XY: 0.353 AC XY: 125 AN XY: 354

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.380 AC: 57791 AN: 152064 Hom.: 11884 Cov.: 33 AF XY: 0.380 AC XY: 28266 AN XY: 74338

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.380

Alfa AF: 0.324 Hom.: 11048

Bravo AF: 0.387

Asia WGS AF: 0.390 AC: 1352 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	1.8
DANN	Benign	0.30

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: rs2906766; hg19: chr7-30499575; COSMIC: COSV56113320;