7-30456766-G-C

Variant names:

• chr7-30456766-G-C
• rs2075818
• NM_006092.4:c.156C>G

Variant summary

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

The NM_006092.4(NOD1):​c.156C>G​(p.Ala52Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,613,648 control chromosomes in the GnomAD database, including 61,307 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 0.32 (8521 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52786 hom.)
• Consequence: NOD1 NM_006092.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 36 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=-0.85).
• BP7: Synonymous conserved (PhyloP=-3.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 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.156C>G	p.Ala52Ala	synonymous	Exon 4 of 14	NP_006083.1	Q9Y239-1
	NOD1	NM_001354849.2		c.156C>G	p.Ala52Ala	synonymous	Exon 4 of 13	NP_001341778.1	Q9Y239-3
	NOD1	NR_149002.2		n.686C>G		non_coding_transcript_exon	Exon 4 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.156C>G	p.Ala52Ala	synonymous	Exon 4 of 14	ENSP00000222823.4	Q9Y239-1
	NOD1	ENST00000411552.5	TSL:1	c.156C>G	p.Ala52Ala	synonymous	Exon 5 of 5	ENSP00000396046.1	A0A1B0GX71
	NOD1	ENST00000413433.5	TSL:1	c.156C>G	p.Ala52Ala	synonymous	Exon 5 of 5	ENSP00000399505.1	A0A1B0GX71

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47922 AN: 151792 Hom.: 8512 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.328

GnomAD2 exomes AF: 0.279 AC: 70221 AN: 251374 AF XY: 0.283

Gnomad AFR exome AF: 0.486

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.262 AC: 382399 AN: 1461738 Hom.: 52786 Cov.: 35 AF XY: 0.265 AC XY: 192759 AN XY: 727186

African (AFR) AF: 0.483 AC: 16180 AN: 33480

American (AMR) AF: 0.160 AC: 7158 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 6478 AN: 26136

East Asian (EAS) AF: 0.413 AC: 16386 AN: 39700

South Asian (SAS) AF: 0.378 AC: 32626 AN: 86252

European-Finnish (FIN) AF: 0.282 AC: 15052 AN: 53404

Middle Eastern (MID) AF: 0.340 AC: 1958 AN: 5754

European-Non Finnish (NFE) AF: 0.243 AC: 269724 AN: 1111900

Other (OTH) AF: 0.279 AC: 16837 AN: 60388

GnomAD4 genome AF: 0.316 AC: 47959 AN: 151910 Hom.: 8521 Cov.: 32 AF XY: 0.318 AC XY: 23639 AN XY: 74266

African (AFR) AF: 0.475 AC: 19673 AN: 41394

American (AMR) AF: 0.205 AC: 3133 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3466

East Asian (EAS) AF: 0.366 AC: 1886 AN: 5158

South Asian (SAS) AF: 0.386 AC: 1861 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2933 AN: 10556

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.247 AC: 16754 AN: 67930

Other (OTH) AF: 0.327 AC: 688 AN: 2106

Alfa AF: 0.224 Hom.: 1346

Bravo AF: 0.317

Asia WGS AF: 0.371 AC: 1287 AN: 3478

EpiCase AF: 0.255

EpiControl AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.040
DANN	Benign	0.37
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2075818; hg19: chr7-30496382; COSMIC: COSV56112566; COSMIC: COSV56112566;