rs3740904

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001378964.1(CDON):c.3294G>A(p.Thr1098Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,598,876 control chromosomes in the GnomAD database, including 109,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10640 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99290 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.325

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

holoprosencephaly 11
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
pituitary stalk interruption syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDON links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 11-125978366-C-T is Benign according to our data. Variant chr11-125978366-C-T is described in ClinVar as Benign. ClinVar VariationId is 260793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.325 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.3294G>A	p.Thr1098Thr	synonymous_variant	Exon 18 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.3294G>A	p.Thr1098Thr	synonymous_variant	Exon 18 of 20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56533

AN:

151750

Hom.:

10624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.360

GnomAD2 exomes

AF:

0.384

AC:

93281

AN:

243128

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.445

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.368

AC:

532225

AN:

1447008

Hom.:

99290

Cov.:

AF XY:

0.369

AC XY:

265159

AN XY:

719560

show subpopulations

African (AFR)

AF:

0.354

AC:

11759

AN:

33258

American (AMR)

AF:

0.440

AC:

19355

AN:

44014

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9222

AN:

26030

East Asian (EAS)

AF:

0.384

AC:

15186

AN:

39576

South Asian (SAS)

AF:

0.401

AC:

33937

AN:

84622

European-Finnish (FIN)

AF:

0.409

AC:

21722

AN:

53110

Middle Eastern (MID)

AF:

0.351

AC:

2010

AN:

5734

European-Non Finnish (NFE)

AF:

0.360

AC:

396375

AN:

1100754

Other (OTH)

AF:

0.378

AC:

22659

AN:

59910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

14929

29858

44788

59717

74646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12668

25336

38004

50672

63340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.373

AC:

56589

AN:

151868

Hom.:

10640

Cov.:

AF XY:

0.378

AC XY:

28048

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.352

AC:

14589

AN:

41400

American (AMR)

AF:

0.428

AC:

6526

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1212

AN:

3460

East Asian (EAS)

AF:

0.389

AC:

2009

AN:

5158

South Asian (SAS)

AF:

0.403

AC:

1938

AN:

4806

European-Finnish (FIN)

AF:

0.427

AC:

4497

AN:

10542

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24658

AN:

67934

Other (OTH)

AF:

0.361

AC:

762

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1840

3680

5519

7359

9199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.364

Hom.:

31328

Bravo

AF:

0.369

Asia WGS

AF:

0.410

AC:

1425

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly 11

Benign:3

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 25, 2018

GeneDx

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

-0.30

CADD

Benign

0.72

(source)

DANN

Benign

0.66

PhyloP100

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over