NM_001378964.1:c.496+50T>C

Variant names:

• chr11-126019569-A-G
• rs75029148
• NM_001378964.1:c.496+50T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.496+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,600,460 control chromosomes in the GnomAD database, including 6,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (593 hom., cov: 32)
  • Exomes 𝑓: 0.089 (6154 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.167
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-126019569-A-G is Benign according to our data. Variant chr11-126019569-A-G is described in ClinVar as [Benign]. Clinvar id is 260802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.496+50T>C		intron_variant	Intron 4 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.496+50T>C		intron_variant	Intron 4 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12110 AN: 152036 Hom.: 592 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.0856

GnomAD2 exomes AF: 0.103 AC: 25756 AN: 250910 AF XY: 0.103

Gnomad AFR exome AF: 0.0268

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0858

Gnomad OTH exome AF: 0.0975

GnomAD4 exome AF: 0.0891 AC: 129109 AN: 1448306 Hom.: 6154 Cov.: 28 AF XY: 0.0901 AC XY: 64970 AN XY: 721414

African (AFR) AF: 0.0251 AC: 834 AN: 33174

American (AMR) AF: 0.136 AC: 6060 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2789 AN: 26048

East Asian (EAS) AF: 0.123 AC: 4870 AN: 39622

South Asian (SAS) AF: 0.120 AC: 10297 AN: 85946

European-Finnish (FIN) AF: 0.125 AC: 6675 AN: 53366

Middle Eastern (MID) AF: 0.0712 AC: 408 AN: 5734

European-Non Finnish (NFE) AF: 0.0833 AC: 91616 AN: 1099766

Other (OTH) AF: 0.0927 AC: 5560 AN: 59976

GnomAD4 genome AF: 0.0797 AC: 12124 AN: 152154 Hom.: 593 Cov.: 32 AF XY: 0.0823 AC XY: 6122 AN XY: 74366

African (AFR) AF: 0.0290 AC: 1206 AN: 41532

American (AMR) AF: 0.118 AC: 1799 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3472

East Asian (EAS) AF: 0.120 AC: 620 AN: 5158

South Asian (SAS) AF: 0.123 AC: 595 AN: 4830

European-Finnish (FIN) AF: 0.127 AC: 1341 AN: 10568

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0875 AC: 5950 AN: 67992

Other (OTH) AF: 0.0894 AC: 189 AN: 2114

Alfa AF: 0.0835 Hom.: 118

Bravo AF: 0.0747

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

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	-0.84
CADD	Benign	6.6
DANN	Benign	0.59
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75029148; hg19: chr11-125889464; COSMIC: COSV54996046; COSMIC: COSV54996046;