rs4426144

Variant names:

• chr11-126018318-C-T
• rs4426144
• NM_001378964.1:c.640+12G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.640+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,611,886 control chromosomes in the GnomAD database, including 7,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (856 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6485 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.488
• Publications: 5 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-126018318-C-T is Benign according to our data. Variant chr11-126018318-C-T is described in ClinVar as Benign. ClinVar VariationId is 260803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 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.640+12G>A		intron	N/A	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.640+12G>A		intron	N/A	NP_001230526.1
	CDON	NM_001441161.1		c.640+12G>A		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.640+12G>A		intron	N/A	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.640+12G>A		intron	N/A	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.640+12G>A		intron	N/A	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15783 AN: 152048 Hom.: 853 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0983

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

GnomAD2 exomes AF: 0.109 AC: 27290 AN: 250998 AF XY: 0.107

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 FIN exome AF: 0.128

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.0993

GnomAD4 exome AF: 0.0918 AC: 133977 AN: 1459720 Hom.: 6485 Cov.: 31 AF XY: 0.0921 AC XY: 66886 AN XY: 726286

African (AFR) AF: 0.112 AC: 3735 AN: 33434

American (AMR) AF: 0.141 AC: 6303 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2688 AN: 26112

East Asian (EAS) AF: 0.123 AC: 4877 AN: 39660

South Asian (SAS) AF: 0.116 AC: 10013 AN: 86208

European-Finnish (FIN) AF: 0.125 AC: 6685 AN: 53372

Middle Eastern (MID) AF: 0.0726 AC: 378 AN: 5206

European-Non Finnish (NFE) AF: 0.0841 AC: 93430 AN: 1110740

Other (OTH) AF: 0.0973 AC: 5868 AN: 60278

GnomAD4 genome AF: 0.104 AC: 15815 AN: 152166 Hom.: 856 Cov.: 32 AF XY: 0.106 AC XY: 7874 AN XY: 74376

African (AFR) AF: 0.114 AC: 4731 AN: 41518

American (AMR) AF: 0.126 AC: 1928 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3468

East Asian (EAS) AF: 0.122 AC: 634 AN: 5184

South Asian (SAS) AF: 0.122 AC: 586 AN: 4814

European-Finnish (FIN) AF: 0.127 AC: 1345 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0878 AC: 5969 AN: 67994

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.0931 Hom.: 249

Bravo AF: 0.102

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	-0.29
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		-0.49
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4426144; hg19: chr11-125888213; COSMIC: COSV54996038; COSMIC: COSV54996038;