chr7-30433407-C-T

Position:

• chr7-30433407-C-T

Variant summary

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

The NM_006092.4(NOD1):​c.2622-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 539,704 control chromosomes in the GnomAD database, including 14,773 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 0.20 (3623 hom., cov: 31)
  • Exomes 𝑓: 0.24 (11150 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD1	NM_006092.4	c.2622-228G>A		intron_variant		ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.2622-228G>A		intron_variant		1	NM_006092.4	ENSP00000222823	P1
NOD1	ENST00000467706.1	n.8G>A		non_coding_transcript_exon_variant	1/3	2
NOD1	ENST00000434755.5	c.*332-228G>A		intron_variant, NMD_transcript_variant		2		ENSP00000416946
NOD1	ENST00000489614.5	n.1838-3950G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30807 AN: 151684 Hom.: 3619 Cov.: 31

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.236 AC: 91482 AN: 387902 Hom.: 11150 Cov.: 2 AF XY: 0.237 AC XY: 48464 AN XY: 204284

Gnomad4 AFR exome AF: 0.0828

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.203 AC: 30813 AN: 151802 Hom.: 3623 Cov.: 31 AF XY: 0.201 AC XY: 14917 AN XY: 74152

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.201

Alfa AF: 0.241 Hom.: 4580

Bravo AF: 0.208

Asia WGS AF: 0.175 AC: 611 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.29

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: rs2907748; hg19: chr7-30473023;