11-126007180-G-T

Variant names:

• chr11-126007180-G-T
• rs528638
• NM_001378964.1:c.1553-1123C>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.1553-1123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,932 control chromosomes in the GnomAD database, including 22,074 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 0.54 (22074 hom., cov: 32)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• 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: 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.1553-1123C>A		intron	N/A	NP_001365893.1
	CDON	NM_001243597.3		c.1553-1123C>A		intron	N/A	NP_001230526.1
	CDON	NM_001441161.1		c.1553-1123C>A		intron	N/A	NP_001428090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.1553-1123C>A		intron	N/A	ENSP00000432901.2
	CDON	ENST00000392693.7	TSL:1	c.1553-1123C>A		intron	N/A	ENSP00000376458.3
	CDON	ENST00000263577.11	TSL:1	c.1553-1123C>A		intron	N/A	ENSP00000263577.7

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81437 AN: 151814 Hom.: 22042 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.537 AC: 81530 AN: 151932 Hom.: 22074 Cov.: 32 AF XY: 0.542 AC XY: 40234 AN XY: 74270

African (AFR) AF: 0.531 AC: 21994 AN: 41406

American (AMR) AF: 0.561 AC: 8567 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2584 AN: 5168

South Asian (SAS) AF: 0.522 AC: 2521 AN: 4826

European-Finnish (FIN) AF: 0.634 AC: 6694 AN: 10558

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35425 AN: 67922

Other (OTH) AF: 0.502 AC: 1057 AN: 2106

Alfa AF: 0.519 Hom.: 40471

Bravo AF: 0.526

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		0.49
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: rs528638; hg19: chr11-125877075;