chr11-126017416-C-T

Variant names:

• chr11-126017416-C-T
• rs7119527
• NM_001378964.1:c.641-41G>A

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.641-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 1,583,714 control chromosomes in the GnomAD database, including 7,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (862 hom., cov: 32)
  • Exomes 𝑓: 0.093 (6402 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0240
• Publications: 3 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=-0.83).
• BP6: Variant 11-126017416-C-T is Benign according to our data. Variant chr11-126017416-C-T is described in ClinVar as Benign. ClinVar VariationId is 260804.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.641-41G>A		intron_variant	Intron 5 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.641-41G>A		intron_variant	Intron 5 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15805 AN: 152104 Hom.: 859 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: 0.122

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.110 AC: 26672 AN: 242854 AF XY: 0.108

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.0867

Gnomad OTH exome AF: 0.0999

GnomAD4 exome AF: 0.0926 AC: 132585 AN: 1431492 Hom.: 6402 Cov.: 26 AF XY: 0.0928 AC XY: 66238 AN XY: 713446

African (AFR) AF: 0.113 AC: 3702 AN: 32884

American (AMR) AF: 0.141 AC: 6247 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2669 AN: 25880

East Asian (EAS) AF: 0.122 AC: 4831 AN: 39454

South Asian (SAS) AF: 0.117 AC: 9903 AN: 84904

European-Finnish (FIN) AF: 0.125 AC: 6668 AN: 53150

Middle Eastern (MID) AF: 0.0716 AC: 409 AN: 5714

European-Non Finnish (NFE) AF: 0.0850 AC: 92331 AN: 1085930

Other (OTH) AF: 0.0980 AC: 5825 AN: 59426

GnomAD4 genome AF: 0.104 AC: 15837 AN: 152222 Hom.: 862 Cov.: 32 AF XY: 0.106 AC XY: 7888 AN XY: 74428

African (AFR) AF: 0.114 AC: 4740 AN: 41518

American (AMR) AF: 0.126 AC: 1924 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3470

East Asian (EAS) AF: 0.122 AC: 630 AN: 5178

South Asian (SAS) AF: 0.122 AC: 591 AN: 4828

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0879 AC: 5981 AN: 68018

Other (OTH) AF: 0.104 AC: 220 AN: 2110

Alfa AF: 0.0922 Hom.: 894

Bravo AF: 0.103

Asia WGS AF: 0.162 AC: 561 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	-0.83
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		0.024
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: rs7119527; hg19: chr11-125887311;