rs3740909

Positions:

chr11-126019631-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378964.1(CDON):c.484G>A(p.Glu162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 1,613,658 control chromosomes in the GnomAD database, including 7,351 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 861 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6490 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.75

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:

CDON (HGNC:):

CDON links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015831888).

BP6

Variant 11-126019631-C-T is Benign according to our data. Variant chr11-126019631-C-T is described in ClinVar as [Benign]. Clinvar id is 260800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126019631-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
CDON	NM_001378964.1 linkuse as main transcript	c.484G>A	p.Glu162Lys	missense_variant	4/20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6 linkuse as main transcript	c.484G>A	p.Glu162Lys	missense_variant	4/20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15774

AN:

151960

Hom.:

858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0982

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

GnomAD3 exomes

AF:

0.109

AC:

27308

AN:

251340

Hom.:

1591

AF XY:

0.107

AC XY:

14494

AN XY:

135830

show subpopulations

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 SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.0859

Gnomad OTH exome

AF:

0.0992

GnomAD4 exome

AF:

0.0919

AC:

134384

AN:

1461580

Hom.:

6490

Cov.:

AF XY:

0.0923

AC XY:

67077

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0844

Gnomad4 OTH exome

AF:

0.0975

GnomAD4 genome

AF:

0.104

AC:

15806

AN:

152078

Hom.:

861

Cov.:

AF XY:

0.106

AC XY:

7867

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.0982

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.0878

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0905

Hom.:

1636

Bravo

AF:

0.103

TwinsUK

AF:

0.0912

AC:

338

ALSPAC

AF:

0.0856

AC:

330

ESP6500AA

AF:

0.124

AC:

545

ESP6500EA

AF:

0.0860

AC:

739

ExAC

AF:

0.106

AC:

12837

Asia WGS

AF:

0.162

AC:

561

AN:

3478

EpiCase

AF:

0.0832

EpiControl

AF:

0.0852

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.32

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.042

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.16

T;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.35

N;N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.18

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.31

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.023

MPC

0.11

ClinPred

0.0059

GERP RS

4.0

Varity_R

0.072

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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