rs4426144

Variant names:

• chr11-126018318-C-T
• rs4426144
• NM_001378964.1:c.640+12G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.640+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,611,886 control chromosomes in the GnomAD database, including 7,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (856 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6485 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.488
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-126018318-C-T is Benign according to our data. Variant chr11-126018318-C-T is described in ClinVar as Benign. ClinVar VariationId is 260803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.640+12G>A		intron_variant	Intron 5 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.640+12G>A		intron_variant	Intron 5 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15783 AN: 152048 Hom.: 853 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.109 AC: 27290 AN: 250998 AF XY: 0.107

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.0993

GnomAD4 exome AF: 0.0918 AC: 133977 AN: 1459720 Hom.: 6485 Cov.: 31 AF XY: 0.0921 AC XY: 66886 AN XY: 726286

African (AFR) AF: 0.112 AC: 3735 AN: 33434

American (AMR) AF: 0.141 AC: 6303 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2688 AN: 26112

East Asian (EAS) AF: 0.123 AC: 4877 AN: 39660

South Asian (SAS) AF: 0.116 AC: 10013 AN: 86208

European-Finnish (FIN) AF: 0.125 AC: 6685 AN: 53372

Middle Eastern (MID) AF: 0.0726 AC: 378 AN: 5206

European-Non Finnish (NFE) AF: 0.0841 AC: 93430 AN: 1110740

Other (OTH) AF: 0.0973 AC: 5868 AN: 60278

GnomAD4 genome AF: 0.104 AC: 15815 AN: 152166 Hom.: 856 Cov.: 32 AF XY: 0.106 AC XY: 7874 AN XY: 74376

African (AFR) AF: 0.114 AC: 4731 AN: 41518

American (AMR) AF: 0.126 AC: 1928 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3468

East Asian (EAS) AF: 0.122 AC: 634 AN: 5184

South Asian (SAS) AF: 0.122 AC: 586 AN: 4814

European-Finnish (FIN) AF: 0.127 AC: 1345 AN: 10590

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5969 AN: 67994

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.0931 Hom.: 249

Bravo AF: 0.102

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Holoprosencephaly 11 Benign:2

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 specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.29
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		-0.49
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4426144; hg19: chr11-125888213; COSMIC: COSV54996038; COSMIC: COSV54996038;