Genetic Variant NM_001378964.1:c.3039C>T (chr11-125981286-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378964.1(CDON):c.3039C>T(p.Asn1013Asn) 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 1,613,168 control chromosomes in the GnomAD database, including 62,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8310 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54407 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.808

Variant links:

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]

CDON links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-125981286-G-A is Benign according to our data. Variant chr11-125981286-G-A is described in ClinVar as [Benign]. Clinvar id is 260791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-125981286-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.808 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.3039C>T	p.Asn1013Asn	synonymous_variant	Exon 17 of 20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6 link	c.3039C>T	p.Asn1013Asn	synonymous_variant	Exon 17 of 20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47789

AN:

151794

Hom.:

8286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.0795

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.256

AC:

64369

AN:

251270

Hom.:

9142

AF XY:

0.252

AC XY:

34254

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.204

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:

390628

AN:

1461256

Hom.:

54407

Cov.:

AF XY:

0.265

AC XY:

192620

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.465

Gnomad4 AMR exome

AF:

0.210

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:

47866

AN:

151912

Hom.:

8310

Cov.:

AF XY:

0.311

AC XY:

23054

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.459

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.0791

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.265

Hom.:

6938

Bravo

AF:

0.317

Asia WGS

AF:

0.206

AC:

716

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.255

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Holoprosencephaly 11

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over