7-30451695-C-T

Variant names:

• chr7-30451695-C-T
• rs2075821
• NM_006092.4:c.1722G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_006092.4(NOD1):​c.1722G>A​(p.Ala574Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,613,604 control chromosomes in the GnomAD database, including 58,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5806 hom., cov: 33)
  • Exomes 𝑓: 0.26 (52646 hom.)
• Consequence: NOD1 NM_006092.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82
• Publications: 28 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-30451695-C-T is Benign according to our data. Variant chr7-30451695-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.1722G>A	p.Ala574Ala	synonymous_variant	Exon 6 of 14	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.1722G>A	p.Ala574Ala	synonymous_variant	Exon 6 of 14	1	NM_006092.4	ENSP00000222823.4
NOD1	ENST00000434755.5	n.1722G>A		non_coding_transcript_exon_variant	Exon 6 of 15	2		ENSP00000416946.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41373 AN: 151942 Hom.: 5801 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.267 AC: 67173 AN: 251172 AF XY: 0.275

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.348

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.264 AC: 385727 AN: 1461544 Hom.: 52646 Cov.: 40 AF XY: 0.268 AC XY: 194776 AN XY: 727094

African (AFR) AF: 0.327 AC: 10963 AN: 33478

American (AMR) AF: 0.152 AC: 6807 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6752 AN: 26136

East Asian (EAS) AF: 0.411 AC: 16299 AN: 39700

South Asian (SAS) AF: 0.373 AC: 32202 AN: 86254

European-Finnish (FIN) AF: 0.243 AC: 12888 AN: 53098

Middle Eastern (MID) AF: 0.330 AC: 1902 AN: 5768

European-Non Finnish (NFE) AF: 0.253 AC: 281485 AN: 1111996

Other (OTH) AF: 0.272 AC: 16429 AN: 60390

GnomAD4 genome AF: 0.272 AC: 41399 AN: 152060 Hom.: 5806 Cov.: 33 AF XY: 0.273 AC XY: 20263 AN XY: 74342

African (AFR) AF: 0.317 AC: 13157 AN: 41464

American (AMR) AF: 0.191 AC: 2921 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1863 AN: 5144

South Asian (SAS) AF: 0.381 AC: 1837 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2486 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17387 AN: 67960

Other (OTH) AF: 0.296 AC: 626 AN: 2116

Alfa AF: 0.256 Hom.: 10284

Bravo AF: 0.270

Asia WGS AF: 0.361 AC: 1253 AN: 3478

EpiCase AF: 0.263

EpiControl AF: 0.267

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.092
DANN	Benign	0.56
PhyloP100		-1.8
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: rs2075821; hg19: chr7-30491311; COSMIC: COSV56112543; COSMIC: COSV56112543;