rs78304400

chr11-125961829-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):c.3526G>A(p.Val1176Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 1,614,134 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (138 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (145 hom.)
• Consequence: CDON NM_001378964.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.43

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021942258).
• BP6: Variant 11-125961829-C-T is Benign according to our data. Variant chr11-125961829-C-T is described in ClinVar as [Benign]. Clinvar id is 260796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.3526G>A	p.Val1176Ile	missense_variant	19/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.3526G>A	p.Val1176Ile	missense_variant	19/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3667 AN: 152128 Hom.: 137 Cov.: 33

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.00719 AC: 1806 AN: 251354 Hom.: 61 AF XY: 0.00559 AC XY: 760 AN XY: 135858

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.00913

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00248

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000748

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00346 AC: 5064 AN: 1461888 Hom.: 145 Cov.: 33 AF XY: 0.00319 AC XY: 2317 AN XY: 727246

Gnomad4 AFR exome AF: 0.0899

Gnomad4 AMR exome AF: 0.00546

Gnomad4 ASJ exome AF: 0.00945

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00253

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.000709

Gnomad4 OTH exome AF: 0.00735

GnomAD4 genome AF: 0.0241 AC: 3672 AN: 152246 Hom.: 138 Cov.: 33 AF XY: 0.0235 AC XY: 1749 AN XY: 74438

Gnomad4 AFR AF: 0.0807

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.00754 Hom.: 34

Bravo AF: 0.0280

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0756 AC: 333

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00866 AC: 1051

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Holoprosencephaly 11 Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.0080
Dann	Benign	0.62
DEOGEN2	Benign	0.20	T;.;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.16	T;T;T
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.090	N;N;N
REVEL	Benign	0.076
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.013
MVP		0.35
MPC		0.078
ClinPred		0.0051	T
GERP RS		-12
Varity_R		0.028
gMVP		0.048

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: rs78304400; hg19: chr11-125831724;