rs6958571

chr7-30446094-A-Cchr7-30446094-A-G

Variant summary

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

The NM_006092.4(NOD1):c.2453+47T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,333,122 control chromosomes in the GnomAD database, including 33,001 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 0.25 (4656 hom., cov: 31)
  • Exomes 𝑓: 0.21 (28345 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.2453+47T>G		intron_variant		ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.2453+47T>G		intron_variant		1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.*163+47T>G		intron_variant, NMD_transcript_variant		2
NOD1	ENST00000489614.5	n.1837+47T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37226 AN: 151130 Hom.: 4655 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.248 AC: 60630 AN: 244370 Hom.: 7952 AF XY: 0.243 AC XY: 32110 AN XY: 132124

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.232

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.174

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.211 AC: 249256 AN: 1181874 Hom.: 28345 Cov.: 17 AF XY: 0.212 AC XY: 127282 AN XY: 599914

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.246 AC: 37231 AN: 151248 Hom.: 4656 Cov.: 31 AF XY: 0.243 AC XY: 17919 AN XY: 73856

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.227

Alfa AF: 0.164 Hom.: 491

Bravo AF: 0.259

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.059
Dann	Benign	0.32

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: rs6958571; hg19: chr7-30485710; COSMIC: COSV56111452;