rs3135500

Variant names:

• chr16-50732975-G-A
• rs3135500
• NM_001370466.1:c.*1156G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-50732975-G-A
• chr16-50732975-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370466.1(NOD2):​c.*1156G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,212 control chromosomes in the GnomAD database, including 15,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15031 hom., cov: 34)
  • Exomes 𝑓: 0.47 (18 hom.)
• Consequence: NOD2 NM_001370466.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.245
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-50732975-G-A is Benign according to our data. Variant chr16-50732975-G-A is described in ClinVar as Benign. ClinVar VariationId is 319492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370466.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	NM_001370466.1	MANE Select	c.*1156G>A		3_prime_UTR	Exon 12 of 12	NP_001357395.1	Q9HC29-2
	NOD2	NM_022162.3		c.*1156G>A		3_prime_UTR	Exon 12 of 12	NP_071445.1	Q9HC29-1
	NOD2	NM_001293557.2		c.*1156G>A		3_prime_UTR	Exon 11 of 11	NP_001280486.1	Q9HC29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	ENST00000647318.2	MANE Select	c.*1156G>A		3_prime_UTR	Exon 12 of 12	ENSP00000495993.1	Q9HC29-2
	NOD2	ENST00000300589.6	TSL:1	c.*1156G>A		3_prime_UTR	Exon 12 of 12	ENSP00000300589.2	Q9HC29-1
	NOD2	ENST00000951248.1		c.*1156G>A		3_prime_UTR	Exon 12 of 12	ENSP00000621307.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66064 AN: 151958 Hom.: 14997 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.471 AC: 64 AN: 136 Hom.: 18 Cov.: 0 AF XY: 0.500 AC XY: 38 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.471 AC: 64 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.435 AC: 66155 AN: 152076 Hom.: 15031 Cov.: 34 AF XY: 0.430 AC XY: 31955 AN XY: 74326

African (AFR) AF: 0.557 AC: 23085 AN: 41464

American (AMR) AF: 0.402 AC: 6138 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1818 AN: 3470

East Asian (EAS) AF: 0.187 AC: 968 AN: 5190

South Asian (SAS) AF: 0.220 AC: 1064 AN: 4826

European-Finnish (FIN) AF: 0.410 AC: 4331 AN: 10554

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27322 AN: 67982

Other (OTH) AF: 0.403 AC: 850 AN: 2108

Alfa AF: 0.401 Hom.: 18356

Bravo AF: 0.440

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autoinflammatory syndrome (1)
-	-	1	Blau syndrome (1)
-	-	1	Inflammatory bowel disease 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.46
PhyloP100		0.24
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: rs3135500; hg19: chr16-50766886;