16-50729814-C-T

Variant names:

• chr16-50729814-C-T
• rs1965389609
• NM_001370466.1:c.2886-4C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001370466.1(NOD2):​c.2886-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: NOD2 NM_001370466.1 splice_region, intron
• Scores: Splicing: ADA: 0.00005847
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.335

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]

CYLD-AS1 (HGNC:55352): (CYLD antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-50729814-C-T is Benign according to our data. Variant chr16-50729814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3750492.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2886-4C>T		splice_region_variant, intron_variant	Intron 10 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2886-4C>T		splice_region_variant, intron_variant	Intron 10 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1458492 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 725582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000901

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Regional enteritis;C5201146:Blau syndrome Benign:1

Nov 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000058
dbscSNV1_RF	Benign	0.022
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

Other links and lift over

dbSNP: rs1965389609; hg19: chr16-50763725;