chr7-30459959-T-C

Variant names:

• chr7-30459959-T-C
• rs2906766
• NM_006092.4:c.-269A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006092.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	NM_006092.4	MANE Select	c.-269A>G		5_prime_UTR	Exon 2 of 14	NP_006083.1	Q9Y239-1
	NOD1	NM_001354849.2		c.-269A>G		5_prime_UTR	Exon 2 of 13	NP_001341778.1	Q9Y239-3
	NOD1	NR_149002.2		n.262A>G		non_coding_transcript_exon	Exon 2 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.-269A>G		5_prime_UTR	Exon 2 of 14	ENSP00000222823.4	Q9Y239-1
	NOD1	ENST00000411552.5	TSL:1	c.-269A>G		5_prime_UTR	Exon 3 of 5	ENSP00000396046.1	A0A1B0GX71
	NOD1	ENST00000413433.5	TSL:1	c.-269A>G		5_prime_UTR	Exon 3 of 5	ENSP00000399505.1	A0A1B0GX71

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

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.345 AC: 147 AN: 426

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.308 AC: 61 AN: 198

Other (OTH) AF: 0.250 AC: 3 AN: 12

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

African (AFR) AF: 0.539 AC: 22339 AN: 41460

American (AMR) AF: 0.316 AC: 4829 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3462

East Asian (EAS) AF: 0.371 AC: 1919 AN: 5170

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4820

European-Finnish (FIN) AF: 0.353 AC: 3733 AN: 10566

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21096 AN: 67992

Other (OTH) AF: 0.380 AC: 802 AN: 2112

Alfa AF: 0.330 Hom.: 14610

Bravo AF: 0.387

Asia WGS AF: 0.390 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.30
PhyloP100		-0.90
Mutation Taster		=296/4	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: rs2906766; hg19: chr7-30499575; COSMIC: COSV56113320;