7-30446094-A-C

Variant names:

• chr7-30446094-A-C
• rs6958571
• NM_006092.4:c.2453+47T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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=-0.82).
• 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 rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.2453+47T>G		intron_variant	Intron 9 of 13	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.2453+47T>G		intron_variant	Intron 9 of 13	1	NM_006092.4	ENSP00000222823.4
NOD1	ENST00000434755.5	n.*163+47T>G		intron_variant	Intron 9 of 14	2		ENSP00000416946.1
NOD1	ENST00000489614.5	n.1837+47T>G		intron_variant	Intron 1 of 2	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

GnomAD2 exomes AF: 0.248 AC: 60630 AN: 244370 AF XY: 0.243

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.216 AC: 6215 AN: 28720

American (AMR) AF: 0.352 AC: 15124 AN: 43006

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 5685 AN: 23692

East Asian (EAS) AF: 0.205 AC: 7650 AN: 37336

South Asian (SAS) AF: 0.208 AC: 16749 AN: 80404

European-Finnish (FIN) AF: 0.172 AC: 9003 AN: 52204

Middle Eastern (MID) AF: 0.172 AC: 903 AN: 5242

European-Non Finnish (NFE) AF: 0.206 AC: 177259 AN: 860306

Other (OTH) AF: 0.209 AC: 10668 AN: 50964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.240 AC: 9911 AN: 41252

American (AMR) AF: 0.301 AC: 4567 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3462

East Asian (EAS) AF: 0.220 AC: 1128 AN: 5116

South Asian (SAS) AF: 0.204 AC: 979 AN: 4792

European-Finnish (FIN) AF: 0.182 AC: 1903 AN: 10484

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 16967 AN: 67664

Other (OTH) AF: 0.227 AC: 477 AN: 2102

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
PhyloP100		-2.8
Mutation Taster		=13/87	disease causing (long InDel)

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