rs2075820

Positions:

• chr7-30452621-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006092.4(NOD1):​c.796G>A​(p.Glu266Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,520 control chromosomes in the GnomAD database, including 56,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.28 (6555 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50224 hom.)
• Consequence: NOD1 NM_006092.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011029333).
• BP6: Variant 7-30452621-C-T is Benign according to our data. Variant chr7-30452621-C-T is described in ClinVar as [Benign]. Clinvar id is 1235615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD1	NM_006092.4	c.796G>A	p.Glu266Lys	missense_variant	6/14	ENST00000222823.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD1	ENST00000222823.9	c.796G>A	p.Glu266Lys	missense_variant	6/14	1	NM_006092.4	P1
NOD1	ENST00000434755.5	c.796G>A	p.Glu266Lys	missense_variant, NMD_transcript_variant	6/15	2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43166 AN: 152106 Hom.: 6549 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.269 AC: 67586 AN: 250900 Hom.: 9839 AF XY: 0.275 AC XY: 37343 AN XY: 135740

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.350

Gnomad SAS exome AF: 0.375

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.257 AC: 375056 AN: 1461296 Hom.: 50224 Cov.: 38 AF XY: 0.261 AC XY: 189383 AN XY: 726966

Gnomad4 AFR exome AF: 0.372

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.412

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.284 AC: 43195 AN: 152224 Hom.: 6555 Cov.: 33 AF XY: 0.286 AC XY: 21291 AN XY: 74412

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.301

Alfa AF: 0.257 Hom.: 10628

Bravo AF: 0.281

TwinsUK AF: 0.239 AC: 888

ALSPAC AF: 0.235 AC: 905

ESP6500AA AF: 0.379 AC: 1670

ESP6500EA AF: 0.245 AC: 2110

ExAC AF: 0.277 AC: 33593

Asia WGS AF: 0.367 AC: 1274 AN: 3478

EpiCase AF: 0.252

EpiControl AF: 0.257

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2021

This variant is associated with the following publications: (PMID: 17309748, 19538217, 19882212) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.99	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.22
Sift	Benign	0.044	D
Sift4G	Uncertain	0.043	D
Polyphen		0.90	P
Vest4		0.069
MPC		0.18
ClinPred		0.011	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.46

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: rs2075820; hg19: chr7-30492237; COSMIC: COSV56111634; COSMIC: COSV56111634;