11-125957080-C-A

Variant names:

• chr11-125957080-C-A
• rs73019367
• NM_001378964.1:c.*3862G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001378964.1(CDON):​c.*3862G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 155,738 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (139 hom., cov: 32)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.321
• 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]

VSIG10L2 (HGNC:27879): (V-set and immunoglobulin domain containing 10 like 2) Predicted to enable cell adhesion molecule binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be active in cell-cell junction. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-125957080-C-A is Benign according to our data. Variant chr11-125957080-C-A is described in ClinVar as [Benign]. Clinvar id is 303379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0368 (5598/152212) while in subpopulation AFR AF = 0.0475 (1972/41508). AF 95% confidence interval is 0.0458. There are 139 homozygotes in GnomAd4. There are 2783 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5598 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.*3862G>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.*3862G>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5573 AN: 152094 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0250 AC: 88 AN: 3526 Hom.: 0 Cov.: 3 AF XY: 0.0205 AC XY: 37 AN XY: 1804

African (AFR) AF: 0.0185 AC: 1 AN: 54

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.0417 AC: 1 AN: 24

East Asian (EAS) AF: 0.0500 AC: 1 AN: 20

South Asian (SAS) AF: 0.00 AC: 0 AN: 68

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.0257 AC: 83 AN: 3232

Other (OTH) AF: 0.0185 AC: 2 AN: 108

GnomAD4 genome AF: 0.0368 AC: 5598 AN: 152212 Hom.: 139 Cov.: 32 AF XY: 0.0374 AC XY: 2783 AN XY: 74404

African (AFR) AF: 0.0475 AC: 1972 AN: 41508

American (AMR) AF: 0.0208 AC: 318 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5180

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4822

European-Finnish (FIN) AF: 0.0831 AC: 881 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1943 AN: 68026

Other (OTH) AF: 0.0341 AC: 72 AN: 2110

Alfa AF: 0.0239 Hom.: 18

Bravo AF: 0.0331

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Holoprosencephaly 11 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.73
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73019367; hg19: chr11-125826975;