11-126035363-C-T

Variant names:

• chr11-126035363-C-T
• rs472926
• NM_001378964.1:c.-61-11826G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378964.1(CDON):​c.-61-11826G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,232 control chromosomes in the GnomAD database, including 58,708 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58708 hom., cov: 32)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.-61-11826G>A		intron_variant	Intron 1 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.-61-11826G>A		intron_variant	Intron 1 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133309 AN: 152114 Hom.: 58643 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.854

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.877 AC: 133433 AN: 152232 Hom.: 58708 Cov.: 32 AF XY: 0.876 AC XY: 65158 AN XY: 74420

African (AFR) AF: 0.970 AC: 40330 AN: 41568

American (AMR) AF: 0.827 AC: 12649 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4333 AN: 5170

South Asian (SAS) AF: 0.817 AC: 3934 AN: 4816

European-Finnish (FIN) AF: 0.835 AC: 8849 AN: 10600

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57422 AN: 68004

Other (OTH) AF: 0.854 AC: 1800 AN: 2108

Alfa AF: 0.853 Hom.: 84350

Bravo AF: 0.879

Asia WGS AF: 0.831 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.77
PhyloP100		-1.7
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: rs472926; hg19: chr11-125905258;