chr11-125957023-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001378964.1(CDON):​c.*3919T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 238,100 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0031 ( 3 hom. )

Consequence

CDON
NM_001378964.1 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0110
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 11-125957023-A-G is Benign according to our data. Variant chr11-125957023-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 303376.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00377 (574/152326) while in subpopulation NFE AF= 0.00422 (287/68028). AF 95% confidence interval is 0.00382. There are 3 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 574 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDONNM_001378964.1 linkuse as main transcriptc.*3919T>C 3_prime_UTR_variant 20/20 ENST00000531738.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDONENST00000531738.6 linkuse as main transcriptc.*3919T>C 3_prime_UTR_variant 20/201 NM_001378964.1 P1Q4KMG0-2
CDONENST00000392693.7 linkuse as main transcriptc.*3919T>C 3_prime_UTR_variant 20/201 Q4KMG0-1
VSIG10L2ENST00000638636.2 linkuse as main transcriptc.*1109A>G 3_prime_UTR_variant 10/105 A2
CDONENST00000684078.1 linkuse as main transcriptc.*3919T>C 3_prime_UTR_variant 20/20 Q4KMG0-1

Frequencies

GnomAD3 genomes
AF:
0.00378
AC:
575
AN:
152208
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000627
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.0423
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00358
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00423
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.00315
AC:
270
AN:
85774
Hom.:
3
Cov.:
5
AF XY:
0.00324
AC XY:
134
AN XY:
41338
show subpopulations
Gnomad4 AFR exome
AF:
0.00205
Gnomad4 AMR exome
AF:
0.0114
Gnomad4 ASJ exome
AF:
0.0370
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00293
Gnomad4 OTH exome
AF:
0.00522
GnomAD4 genome
AF:
0.00377
AC:
574
AN:
152326
Hom.:
3
Cov.:
33
AF XY:
0.00364
AC XY:
271
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000625
Gnomad4 AMR
AF:
0.00418
Gnomad4 ASJ
AF:
0.0423
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00358
Gnomad4 NFE
AF:
0.00422
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00482
Hom.:
3
Bravo
AF:
0.00400
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Holoprosencephaly 11 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
4.1
DANN
Benign
0.54

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61917811; hg19: chr11-125826918; API