7-30451144-A-G

Variant names:

• chr7-30451144-A-G
• rs2075822
• NM_006092.4:c.2201+72T>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.2201+72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,512,272 control chromosomes in the GnomAD database, including 37,186 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 0.19 (3034 hom., cov: 32)
  • Exomes 𝑓: 0.22 (34152 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 15 publications found

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006092.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	NM_006092.4	MANE Select	c.2201+72T>C		intron	N/A	NP_006083.1
	NOD1	NM_001354849.2		c.2201+72T>C		intron	N/A	NP_001341778.1
	NOD1	NR_149002.2		n.2731+72T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.2201+72T>C		intron	N/A	ENSP00000222823.4
	NOD1	ENST00000434755.5	TSL:2	n.2201+72T>C		intron	N/A	ENSP00000416946.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29132 AN: 152028 Hom.: 3034 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.221 AC: 300694 AN: 1360126 Hom.: 34152 AF XY: 0.220 AC XY: 147719 AN XY: 671836

African (AFR) AF: 0.101 AC: 3176 AN: 31518

American (AMR) AF: 0.324 AC: 11969 AN: 36974

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 5559 AN: 21974

East Asian (EAS) AF: 0.216 AC: 8312 AN: 38558

South Asian (SAS) AF: 0.204 AC: 15340 AN: 75318

European-Finnish (FIN) AF: 0.167 AC: 6975 AN: 41882

Middle Eastern (MID) AF: 0.159 AC: 745 AN: 4680

European-Non Finnish (NFE) AF: 0.225 AC: 236697 AN: 1052668

Other (OTH) AF: 0.211 AC: 11921 AN: 56554

GnomAD4 genome AF: 0.191 AC: 29129 AN: 152146 Hom.: 3034 Cov.: 32 AF XY: 0.192 AC XY: 14277 AN XY: 74396

African (AFR) AF: 0.110 AC: 4562 AN: 41510

American (AMR) AF: 0.261 AC: 3990 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3466

East Asian (EAS) AF: 0.225 AC: 1161 AN: 5168

South Asian (SAS) AF: 0.192 AC: 929 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10584

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14913 AN: 67990

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.210 Hom.: 1426

Bravo AF: 0.196

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.38
PhyloP100		-0.76
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

Other links and lift over

dbSNP: rs2075822; hg19: chr7-30490760; COSMIC: COSV56115628; COSMIC: COSV56115628;