11-126005939-C-T

Position:

chr11-126005939-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001378964.1(CDON):c.1671G>A(p.Lys557=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,614,058 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 33 hom., cov: 32)

Exomes 𝑓: 0.023 ( 435 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0280

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]

CDON links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 11-126005939-C-T is Benign according to our data. Variant chr11-126005939-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126005939-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.028 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2586/152212) while in subpopulation NFE AF= 0.0263 (1785/67996). AF 95% confidence interval is 0.0252. There are 33 homozygotes in gnomad4. There are 1235 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2586 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1 linkuse as main transcript	c.1671G>A	p.Lys557=	synonymous_variant	9/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6 linkuse as main transcript	c.1671G>A	p.Lys557=	synonymous_variant	9/20	1	NM_001378964.1	P1	Q4KMG0-2

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2586

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00406

Gnomad AMI

AF:

0.0319

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0326

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0181

AC:

4544

AN:

251110

Hom.:

AF XY:

0.0182

AC XY:

2464

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.00954

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00630

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0266

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0229

AC:

33517

AN:

1461846

Hom.:

435

Cov.:

AF XY:

0.0223

AC XY:

16231

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00338

Gnomad4 AMR exome

AF:

0.00937

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00636

Gnomad4 FIN exome

AF:

0.0322

Gnomad4 NFE exome

AF:

0.0261

Gnomad4 OTH exome

AF:

0.0199

GnomAD4 genome

AF:

0.0170

AC:

2586

AN:

152212

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1235

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00404

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.0326

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0235

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0234

EpiControl

AF:

0.0247

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 28, 2018	- -

Holoprosencephaly 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.1

DANN

Benign

0.46

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over