rs3135499

Variant names:

• chr16-50732216-A-C
• rs3135499
• NM_001370466.1:c.*397A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-50732216-A-C
• chr16-50732216-A-G

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.*397A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 353,018 control chromosomes in the GnomAD database, including 30,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15644 hom., cov: 30)
  • Exomes 𝑓: 0.38 (15321 hom.)
• Consequence: NOD2 NM_001370466.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.931
• Publications: 48 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=-0.93).
• BP6: Variant 16-50732216-A-C is Benign according to our data. Variant chr16-50732216-A-C is described in ClinVar as Benign. ClinVar VariationId is 319482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 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.*397A>C		3_prime_UTR	Exon 12 of 12	NP_001357395.1	Q9HC29-2
	NOD2	NM_022162.3		c.*397A>C		3_prime_UTR	Exon 12 of 12	NP_071445.1	Q9HC29-1
	NOD2	NM_001293557.2		c.*397A>C		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.*397A>C		3_prime_UTR	Exon 12 of 12	ENSP00000495993.1	Q9HC29-2
	NOD2	ENST00000300589.6	TSL:1	c.*397A>C		3_prime_UTR	Exon 12 of 12	ENSP00000300589.2	Q9HC29-1
	NOD2	ENST00000951248.1		c.*397A>C		3_prime_UTR	Exon 12 of 12	ENSP00000621307.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67416 AN: 151636 Hom.: 15619 Cov.: 30

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.377 AC: 75867 AN: 201264 Hom.: 15321 Cov.: 0 AF XY: 0.363 AC XY: 39328 AN XY: 108376

African (AFR) AF: 0.561 AC: 3310 AN: 5904

American (AMR) AF: 0.353 AC: 3612 AN: 10218

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 2645 AN: 5036

East Asian (EAS) AF: 0.219 AC: 2209 AN: 10090

South Asian (SAS) AF: 0.253 AC: 8859 AN: 35056

European-Finnish (FIN) AF: 0.427 AC: 4339 AN: 10170

Middle Eastern (MID) AF: 0.429 AC: 310 AN: 722

European-Non Finnish (NFE) AF: 0.408 AC: 46494 AN: 113824

Other (OTH) AF: 0.399 AC: 4089 AN: 10244

GnomAD4 genome AF: 0.445 AC: 67495 AN: 151754 Hom.: 15644 Cov.: 30 AF XY: 0.440 AC XY: 32618 AN XY: 74162

African (AFR) AF: 0.556 AC: 23006 AN: 41354

American (AMR) AF: 0.404 AC: 6163 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1845 AN: 3470

East Asian (EAS) AF: 0.189 AC: 970 AN: 5128

South Asian (SAS) AF: 0.228 AC: 1095 AN: 4812

European-Finnish (FIN) AF: 0.432 AC: 4550 AN: 10542

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28417 AN: 67894

Other (OTH) AF: 0.411 AC: 863 AN: 2098

Alfa AF: 0.422 Hom.: 59568

Bravo AF: 0.448

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Blau syndrome (1)
-	-	1	Inflammatory bowel disease 1 (1)
-	1	-	Leprosy, susceptibility to, 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.3
DANN	Benign	0.37
PhyloP100		-0.93
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: rs3135499; hg19: chr16-50766127; COSMIC: COSV56051520; COSMIC: COSV56051520;