Genetic Variant NM_001378964.1:c.76+21G>A (chr11-126023380-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001378964.1(CDON):c.76+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,515,102 control chromosomes in the GnomAD database, including 26,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2384 hom., cov: 32)

Exomes 𝑓: 0.19 ( 24548 hom. )

Consequence

CDON
NM_001378964.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.27

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 (BayesDel_noAF=-0.91).

BP6

Variant 11-126023380-C-T is Benign according to our data. Variant chr11-126023380-C-T is described in ClinVar as [Benign]. Clinvar id is 260805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.76+21G>A		intron_variant	Intron 2 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6 link	c.76+21G>A		intron_variant	Intron 2 of 19	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25891

AN:

151860

Hom.:

2384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.183

AC:

46041

AN:

251086

Hom.:

4272

AF XY:

0.184

AC XY:

25034

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.187

AC:

255288

AN:

1363124

Hom.:

24548

Cov.:

AF XY:

0.188

AC XY:

128550

AN XY:

684154

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.171

AC:

25918

AN:

151978

Hom.:

2384

Cov.:

AF XY:

0.171

AC XY:

12690

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.177

Hom.:

3513

Bravo

AF:

0.163

Asia WGS

AF:

0.229

AC:

796

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.91

CADD

Benign

0.35

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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