rs2907749

Variant names:

• chr7-30446125-A-G
• rs2907749
• NM_006092.4:c.2453+16T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006092.4(NOD1):​c.2453+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,592,430 control chromosomes in the GnomAD database, including 72,342 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 0.35 (9927 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62415 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.91

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.2453+16T>C		intron_variant	Intron 9 of 13	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.2453+16T>C		intron_variant	Intron 9 of 13	1	NM_006092.4	ENSP00000222823.4
NOD1	ENST00000434755.5	n.*163+16T>C		intron_variant	Intron 9 of 14	2		ENSP00000416946.1
NOD1	ENST00000489614.5	n.1837+16T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52327 AN: 151732 Hom.: 9897 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.319

GnomAD2 exomes AF: 0.301 AC: 75524 AN: 251288 AF XY: 0.293

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.277

GnomAD4 exome AF: 0.288 AC: 415431 AN: 1440580 Hom.: 62415 Cov.: 27 AF XY: 0.286 AC XY: 205494 AN XY: 717884

Gnomad4 AFR exome AF: 0.506 AC: 16752 AN: 33134

Gnomad4 AMR exome AF: 0.385 AC: 17180 AN: 44632

Gnomad4 ASJ exome AF: 0.294 AC: 7631 AN: 25930

Gnomad4 EAS exome AF: 0.220 AC: 8672 AN: 39498

Gnomad4 SAS exome AF: 0.263 AC: 22544 AN: 85880

Gnomad4 FIN exome AF: 0.188 AC: 10001 AN: 53276

Gnomad4 NFE exome AF: 0.287 AC: 313589 AN: 1092806

Gnomad4 Remaining exome AF: 0.292 AC: 17408 AN: 59686

GnomAD4 genome AF: 0.345 AC: 52392 AN: 151850 Hom.: 9927 Cov.: 32 AF XY: 0.338 AC XY: 25108 AN XY: 74212

Gnomad4 AFR AF: 0.507 AC: 0.506592 AN: 0.506592

Gnomad4 AMR AF: 0.353 AC: 0.352721 AN: 0.352721

Gnomad4 ASJ AF: 0.285 AC: 0.285055 AN: 0.285055

Gnomad4 EAS AF: 0.225 AC: 0.225087 AN: 0.225087

Gnomad4 SAS AF: 0.246 AC: 0.24647 AN: 0.24647

Gnomad4 FIN AF: 0.190 AC: 0.190214 AN: 0.190214

Gnomad4 NFE AF: 0.287 AC: 0.28655 AN: 0.28655

Gnomad4 OTH AF: 0.315 AC: 0.315166 AN: 0.315166

Alfa AF: 0.308 Hom.: 4521

Bravo AF: 0.366

Asia WGS AF: 0.210 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0070
DANN	Benign	0.39
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

Publications

LitVar

Other links and lift over

dbSNP: rs2907749; hg19: chr7-30485741; COSMIC: COSV56111455;