rs11826465

Variant names:

• chr11-126019574-G-A
• rs11826465
• NM_001378964.1:c.496+45C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-126019574-G-A
• chr11-126019574-G-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+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,604,274 control chromosomes in the GnomAD database, including 7,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (855 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6481 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0740
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-126019574-G-A is Benign according to our data. Variant chr11-126019574-G-A is described in ClinVar as Benign. ClinVar VariationId is 260801.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.496+45C>T		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+45C>T		intron_variant	Intron 4 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15813 AN: 151974 Hom.: 852 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.110 AC: 27488 AN: 251018 AF XY: 0.108

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.0862

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0918 AC: 133371 AN: 1452182 Hom.: 6481 Cov.: 29 AF XY: 0.0924 AC XY: 66807 AN XY: 723086

African (AFR) AF: 0.111 AC: 3695 AN: 33264

American (AMR) AF: 0.141 AC: 6306 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2793 AN: 26068

East Asian (EAS) AF: 0.123 AC: 4869 AN: 39648

South Asian (SAS) AF: 0.120 AC: 10326 AN: 86032

European-Finnish (FIN) AF: 0.125 AC: 6682 AN: 53370

Middle Eastern (MID) AF: 0.0744 AC: 428 AN: 5750

European-Non Finnish (NFE) AF: 0.0837 AC: 92389 AN: 1103262

Other (OTH) AF: 0.0979 AC: 5883 AN: 60098

GnomAD4 genome AF: 0.104 AC: 15845 AN: 152092 Hom.: 855 Cov.: 32 AF XY: 0.106 AC XY: 7887 AN XY: 74350

African (AFR) AF: 0.114 AC: 4728 AN: 41476

American (AMR) AF: 0.126 AC: 1928 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.121 AC: 625 AN: 5168

South Asian (SAS) AF: 0.123 AC: 596 AN: 4826

European-Finnish (FIN) AF: 0.127 AC: 1342 AN: 10574

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5980 AN: 67988

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

Alfa AF: 0.0932 Hom.: 229

Bravo AF: 0.103

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.97
CADD	Benign	5.9
DANN	Benign	0.64
PhyloP100		-0.074
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: rs11826465; hg19: chr11-125889469; COSMIC: COSV54996055; COSMIC: COSV54996055;