11-125981160-A-G

Position:

• chr11-125981160-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378964.1(CDON):​c.3165T>C​(p.Asn1055=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,738 control chromosomes in the GnomAD database, including 62,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8301 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54422 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.91

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-125981160-A-G is Benign according to our data. Variant chr11-125981160-A-G is described in ClinVar as [Benign]. Clinvar id is 260792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-125981160-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.3165T>C	p.Asn1055=	synonymous_variant	17/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.3165T>C	p.Asn1055=	synonymous_variant	17/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47772 AN: 151872 Hom.: 8277 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.272

GnomAD3 exomes AF: 0.256 AC: 64400 AN: 251404 Hom.: 9156 AF XY: 0.252 AC XY: 34266 AN XY: 135868

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.0800

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.267 AC: 390877 AN: 1461748 Hom.: 54422 Cov.: 37 AF XY: 0.265 AC XY: 192727 AN XY: 727180

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.0795

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.315 AC: 47849 AN: 151990 Hom.: 8301 Cov.: 32 AF XY: 0.310 AC XY: 23040 AN XY: 74286

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.275

Alfa AF: 0.266 Hom.: 3318

Bravo AF: 0.318

Asia WGS AF: 0.206 AC: 717 AN: 3478

EpiCase AF: 0.256

EpiControl AF: 0.256

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Holoprosencephaly 11 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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	Benign	-0.86
CADD	Benign	0.022
DANN	Benign	0.31

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: rs564214; hg19: chr11-125851055; COSMIC: COSV54998321;