Genetic Variant NOD1:p.Ala574Ala (chr7-30451695-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.82

Variant links:

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]

NOD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.1722G>A	p.Ala574Ala	synonymous_variant	Exon 6 of 14	ENST00000222823.9	NP_006083.1	Q9Y239-1A0A024RA73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9 link	c.1722G>A	p.Ala574Ala	synonymous_variant	Exon 6 of 14	1	NM_006092.4	ENSP00000222823.4		Q9Y239-1
NOD1	ENST00000434755.5 link	n.1722G>A		non_coding_transcript_exon_variant	Exon 6 of 15	2		ENSP00000416946.1		G3XAL1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41373

AN:

151942

Hom.:

5801

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.267

AC:

67173

AN:

251172

Hom.:

9519

AF XY:

0.275

AC XY:

37333

AN XY:

135844

show subpopulations

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 SAS exome

AF:

0.373

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.:

AF XY:

0.268

AC XY:

194776

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.373

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.272

AC:

41399

AN:

152060

Hom.:

5806

Cov.:

AF XY:

0.273

AC XY:

20263

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.256

Hom.:

8422

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

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over