rs2075820

Variant names:

• chr7-30452621-C-T
• rs2075820
• NM_006092.4:c.796G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Publications: 98 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	NM_006092.4	MANE Select	c.796G>A	p.Glu266Lys	missense	Exon 6 of 14	NP_006083.1	Q9Y239-1
	NOD1	NM_001354849.2		c.796G>A	p.Glu266Lys	missense	Exon 6 of 13	NP_001341778.1	Q9Y239-3
	NOD1	NR_149002.2		n.1326G>A		non_coding_transcript_exon	Exon 6 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD1	ENST00000222823.9	TSL:1 MANE Select	c.796G>A	p.Glu266Lys	missense	Exon 6 of 14	ENSP00000222823.4	Q9Y239-1
	NOD1	ENST00000855556.1		c.796G>A	p.Glu266Lys	missense	Exon 7 of 15	ENSP00000525615.1
	NOD1	ENST00000855558.1		c.796G>A	p.Glu266Lys	missense	Exon 7 of 15	ENSP00000525617.1

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

GnomAD2 exomes AF: 0.269 AC: 67586 AN: 250900 AF XY: 0.275

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 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

African (AFR) AF: 0.372 AC: 12458 AN: 33480

American (AMR) AF: 0.152 AC: 6807 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6467 AN: 26136

East Asian (EAS) AF: 0.412 AC: 16363 AN: 39700

South Asian (SAS) AF: 0.375 AC: 32316 AN: 86254

European-Finnish (FIN) AF: 0.280 AC: 14785 AN: 52862

Middle Eastern (MID) AF: 0.330 AC: 1903 AN: 5768

European-Non Finnish (NFE) AF: 0.241 AC: 267779 AN: 1111984

Other (OTH) AF: 0.268 AC: 16178 AN: 60390

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

African (AFR) AF: 0.369 AC: 15306 AN: 41530

American (AMR) AF: 0.191 AC: 2921 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1857 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2927 AN: 10606

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16634 AN: 68000

Other (OTH) AF: 0.301 AC: 636 AN: 2116

Alfa AF: 0.261 Hom.: 21599

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.2
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
Mutation Taster		=92/8	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: rs2075820; hg19: chr7-30492237; COSMIC: COSV56111634; COSMIC: COSV56111634;