7-30449391-A-G

Position:

• chr7-30449391-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.2202-1010T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,172 control chromosomes in the GnomAD database, including 4,874 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 (4874 hom., cov: 32)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.2202-1010T>C		intron_variant		ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.2202-1010T>C		intron_variant		1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.2202-1010T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36637 AN: 152054 Hom.: 4871 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36647 AN: 152172 Hom.: 4874 Cov.: 32 AF XY: 0.237 AC XY: 17606 AN XY: 74394

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.239

Alfa AF: 0.268 Hom.: 1157

Bravo AF: 0.246

Asia WGS AF: 0.192 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.68

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: rs2284358; hg19: chr7-30489007;