Variant 16-50700058-A-G 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.459+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,093,490 control chromosomes in the GnomAD database, including 236,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 32992 hom., cov: 32)

Exomes 𝑓: 0.65 ( 203089 hom. )

Consequence

NOD2
NM_001370466.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.15

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:

NOD2 (HGNC:):

NOD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-50700058-A-G is Benign according to our data. Variant chr16-50700058-A-G is described in ClinVar as [Benign]. Clinvar id is 2688412.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD2	NM_001370466.1 linkuse as main transcript	c.459+104A>G		intron_variant		ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.459+104A>G		intron_variant			NM_001370466.1	ENSP00000495993.1		Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98978

AN:

151980

Hom.:

32987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.791

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.624

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.662

GnomAD4 exome

AF:

0.647

AC:

609201

AN:

941392

Hom.:

203089

AF XY:

0.643

AC XY:

308777

AN XY:

480562

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.799

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.623

Gnomad4 NFE exome

AF:

0.686

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.651

AC:

99032

AN:

152098

Hom.:

32992

Cov.:

AF XY:

0.642

AC XY:

47734

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.791

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.469

Gnomad4 FIN

AF:

0.624

Gnomad4 NFE

AF:

0.697

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.563

Hom.:

2788

Bravo

AF:

0.648

Asia WGS

AF:

0.387

AC:

1349

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

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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