NM_001378964.1:c.350-13T>C

Variant names:

• chr11-126019778-A-G
• rs3740910
• NM_001378964.1:c.350-13T>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.350-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,601,770 control chromosomes in the GnomAD database, including 7,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (863 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6385 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.647
• Publications: 6 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: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.83).
• BP6: Variant 11-126019778-A-G is Benign according to our data. Variant chr11-126019778-A-G is described in ClinVar as Benign. ClinVar VariationId is 260795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.350-13T>C		intron	N/A	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.350-13T>C		intron	N/A	NP_001230526.1
	CDON	NM_001441161.1		c.350-13T>C		intron	N/A	NP_001428090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.350-13T>C		intron	N/A	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.350-13T>C		intron	N/A	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.350-13T>C		intron	N/A	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15804 AN: 152130 Hom.: 860 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.109 AC: 27022 AN: 248602 AF XY: 0.107

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0913 AC: 132284 AN: 1449522 Hom.: 6385 Cov.: 28 AF XY: 0.0916 AC XY: 66124 AN XY: 721940

African (AFR) AF: 0.111 AC: 3687 AN: 33198

American (AMR) AF: 0.141 AC: 6294 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2675 AN: 26068

East Asian (EAS) AF: 0.123 AC: 4856 AN: 39608

South Asian (SAS) AF: 0.116 AC: 9964 AN: 86024

European-Finnish (FIN) AF: 0.125 AC: 6604 AN: 52698

Middle Eastern (MID) AF: 0.0709 AC: 396 AN: 5588

European-Non Finnish (NFE) AF: 0.0835 AC: 91984 AN: 1101694

Other (OTH) AF: 0.0971 AC: 5824 AN: 59972

GnomAD4 genome AF: 0.104 AC: 15836 AN: 152248 Hom.: 863 Cov.: 32 AF XY: 0.106 AC XY: 7888 AN XY: 74450

African (AFR) AF: 0.114 AC: 4737 AN: 41534

American (AMR) AF: 0.126 AC: 1930 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.122 AC: 634 AN: 5182

South Asian (SAS) AF: 0.122 AC: 588 AN: 4822

European-Finnish (FIN) AF: 0.127 AC: 1347 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5978 AN: 68018

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0954 Hom.: 143

Bravo AF: 0.103

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Holoprosencephaly 11 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		-0.65
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: rs3740910; hg19: chr11-125889673; COSMIC: COSV54996157; COSMIC: COSV54996157;