rs5743369

chr7-30428568-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.2789+806A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,198 control chromosomes in the GnomAD database, including 5,840 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 0.24 (5840 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.2789+806A>G		intron_variant		ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.2789+806A>G		intron_variant		1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.*541A>G		3_prime_UTR_variant, NMD_transcript_variant	14/15	2
NOD1	ENST00000467706.1	n.403+806A>G		intron_variant, non_coding_transcript_variant		2
NOD1	ENST00000489614.5	n.1921+806A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35815 AN: 152070 Hom.: 5819 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.236 AC: 35878 AN: 152188 Hom.: 5840 Cov.: 32 AF XY: 0.236 AC XY: 17532 AN XY: 74424

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0766

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.208

Alfa AF: 0.171 Hom.: 1184

Bravo AF: 0.239

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	11
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5743369; hg19: chr7-30468184;