rs3737336

Positions:

• chr11-125960802-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.*140A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.293 in 790,096 control chromosomes in the GnomAD database, including 35,027 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5477 hom., cov: 32)
  • Exomes 𝑓: 0.30 (29550 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.78

Genes affected

CDON (HGNC:17104): (cell adhesion associated, oncogene regulated) This gene encodes a cell surface receptor that is a member of the immunoglobulin superfamily. The encoded protein contains three fibronectin type III domains and five immunoglobulin-like C2-type domains. This protein is a member of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells and positively regulates myogenesis. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-125960802-T-C is Benign according to our data. Variant chr11-125960802-T-C is described in ClinVar as [Benign]. Clinvar id is 303488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.*140A>G		3_prime_UTR_variant	20/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.*140A>G		3_prime_UTR_variant	20/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38761 AN: 152022 Hom.: 5475 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.302 AC: 192349 AN: 637956 Hom.: 29550 Cov.: 8 AF XY: 0.304 AC XY: 103436 AN XY: 340620

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.255 AC: 38780 AN: 152140 Hom.: 5477 Cov.: 32 AF XY: 0.257 AC XY: 19095 AN XY: 74356

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.250

Alfa AF: 0.305 Hom.: 13753

Bravo AF: 0.247

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2019

- -

Holoprosencephaly 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs3737336; hg19: chr11-125830697; COSMIC: COSV54997022; COSMIC: COSV54997022;