ENST00000392693.7:c.*4135C>T

Variant names:

• chr11-125956807-G-A
• rs4937076
• ENST00000392693.7:c.*4135C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000392693.7(CDON):​c.*4135C>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 0.525 in 988,828 control chromosomes in the GnomAD database, including 137,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19124 hom., cov: 32)
  • Exomes 𝑓: 0.53 (118801 hom.)
• Consequence: CDON ENST00000392693.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03
• Publications: 9 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=-0.91).
• BP6: Variant 11-125956807-G-A is Benign according to our data. Variant chr11-125956807-G-A is described in ClinVar as [Benign]. Clinvar id is 368942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.*4135C>T		downstream_gene_variant		ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000392693.7	c.*4135C>T		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000376458.3
CDON	ENST00000684078.1	c.*4135C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000507318.1
VSIG10L2	ENST00000638636.2	c.*893G>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000491467.1
CDON	ENST00000531738.6	c.*4135C>T		downstream_gene_variant		1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74575 AN: 151888 Hom.: 19117 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.506

GnomAD4 exome AF: 0.531 AC: 444740 AN: 836822 Hom.: 118801 Cov.: 33 AF XY: 0.531 AC XY: 205419 AN XY: 386672

African (AFR) AF: 0.335 AC: 5294 AN: 15814

American (AMR) AF: 0.431 AC: 743 AN: 1724

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 2859 AN: 5182

East Asian (EAS) AF: 0.714 AC: 2639 AN: 3696

South Asian (SAS) AF: 0.520 AC: 8685 AN: 16694

European-Finnish (FIN) AF: 0.579 AC: 191 AN: 330

Middle Eastern (MID) AF: 0.537 AC: 875 AN: 1628

European-Non Finnish (NFE) AF: 0.535 AC: 408681 AN: 764278

Other (OTH) AF: 0.538 AC: 14773 AN: 27476

GnomAD4 genome AF: 0.491 AC: 74609 AN: 152006 Hom.: 19124 Cov.: 32 AF XY: 0.496 AC XY: 36860 AN XY: 74280

African (AFR) AF: 0.351 AC: 14564 AN: 41456

American (AMR) AF: 0.473 AC: 7230 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3468

East Asian (EAS) AF: 0.707 AC: 3637 AN: 5142

South Asian (SAS) AF: 0.523 AC: 2522 AN: 4824

European-Finnish (FIN) AF: 0.621 AC: 6567 AN: 10572

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36526 AN: 67942

Other (OTH) AF: 0.503 AC: 1062 AN: 2110

Alfa AF: 0.521 Hom.: 53797

Bravo AF: 0.477

Asia WGS AF: 0.567 AC: 1968 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Holoprosencephaly sequence Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.60
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4937076; hg19: chr11-125826702;