Variant 16-50699463-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001370466.1(NOD2):c.-8-25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,603,308 control chromosomes in the GnomAD database, including 55,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3671 hom., cov: 31)

Exomes 𝑓: 0.26 ( 51718 hom. )

Consequence

NOD2
NM_001370466.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.412

Variant links:

Genes affected

NOD2 (HGNC:5331): (nucleotide binding oligomerization domain containing 2) This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

NOD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-50699463-G-T is Benign according to our data. Variant chr16-50699463-G-T is described in ClinVar as [Benign]. Clinvar id is 2628228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD2	NM_001370466.1 linkuse as main transcript	c.-8-25G>T		intron_variant		ENST00000647318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.-8-25G>T		intron_variant			NM_001370466.1	P1	Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29637

AN:

151920

Hom.:

3670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.00889

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.201

AC:

49930

AN:

248254

Hom.:

6355

AF XY:

0.209

AC XY:

28110

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.0692

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.00637

Gnomad SAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.255

AC:

370354

AN:

1451270

Hom.:

51718

Cov.:

AF XY:

0.254

AC XY:

183388

AN XY:

722426

show subpopulations

Gnomad4 AFR exome

AF:

0.0674

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.00353

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.195

AC:

29645

AN:

152038

Hom.:

3671

Cov.:

AF XY:

0.190

AC XY:

14152

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.00891

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.186

Hom.:

799

Bravo

AF:

0.188

Asia WGS

AF:

0.0750

AC:

268

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.3

DANN

Benign

0.81

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