11-125961075-A-T

Position:

chr11-125961075-A-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.3662T>A(p.Ile1221Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,132 control chromosomes in the GnomAD database, including 403,270 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 0.75 ( 42774 hom., cov: 33)

Exomes 𝑓: 0.70 ( 360496 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.447

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.3759915E-6).

BP6

Variant 11-125961075-A-T is Benign according to our data. Variant chr11-125961075-A-T is described in ClinVar as [Benign]. Clinvar id is 260799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-125961075-A-T is described in Lovd as [Benign]. Variant chr11-125961075-A-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1 linkuse as main transcript	c.3662T>A	p.Ile1221Asn	missense_variant	20/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6 linkuse as main transcript	c.3662T>A	p.Ile1221Asn	missense_variant	20/20	1	NM_001378964.1	P1	Q4KMG0-2

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113304

AN:

151982

Hom.:

42730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.528

Gnomad AMR

AF:

0.770

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.923

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.732

AC:

183804

AN:

251040

Hom.:

67937

AF XY:

0.727

AC XY:

98695

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.844

Gnomad AMR exome

AF:

0.784

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.925

Gnomad SAS exome

AF:

0.722

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.733

GnomAD4 exome

AF:

0.700

AC:

1023018

AN:

1461030

Hom.:

360496

Cov.:

AF XY:

0.700

AC XY:

509011

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.847

Gnomad4 AMR exome

AF:

0.780

Gnomad4 ASJ exome

AF:

0.732

Gnomad4 EAS exome

AF:

0.930

Gnomad4 SAS exome

AF:

0.722

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.746

AC:

113406

AN:

152102

Hom.:

42774

Cov.:

AF XY:

0.748

AC XY:

55582

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.841

Gnomad4 AMR

AF:

0.770

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.923

Gnomad4 SAS

AF:

0.739

Gnomad4 FIN

AF:

0.694

Gnomad4 NFE

AF:

0.680

Gnomad4 OTH

AF:

0.741

Alfa

AF:

0.698

Hom.:

12090

Bravo

AF:

0.759

TwinsUK

AF:

0.675

AC:

2502

ALSPAC

AF:

0.684

AC:

2637

ESP6500AA

AF:

0.826

AC:

3635

ESP6500EA

AF:

0.681

AC:

5855

ExAC

AF:

0.731

AC:

88720

Asia WGS

AF:

0.802

AC:

2788

AN:

3478

EpiCase

AF:

0.695

EpiControl

AF:

0.692

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Holoprosencephaly 11

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Holoprosencephaly 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

DANN

Benign

0.48

DEOGEN2

Benign

0.20

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.0000044

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.0

N;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

2.5

N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.16

MPC

0.17

ClinPred

0.0014

GERP RS

4.3

Varity_R

0.027

gMVP

0.071

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