rs564214

Variant names:

• chr11-125981160-A-G
• rs564214
• NM_001378964.1:c.3165T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-125981160-A-G
• chr11-125981160-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378964.1(CDON):​c.3165T>C​(p.Asn1055Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,738 control chromosomes in the GnomAD database, including 62,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8301 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54422 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.91
• Publications: 20 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: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-125981160-A-G is Benign according to our data. Variant chr11-125981160-A-G is described in ClinVar as Benign. ClinVar VariationId is 260792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.3165T>C	p.Asn1055Asn	synonymous	Exon 17 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.3165T>C	p.Asn1055Asn	synonymous	Exon 17 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.3165T>C	p.Asn1055Asn	synonymous	Exon 17 of 20	NP_001428090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.3165T>C	p.Asn1055Asn	synonymous	Exon 17 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.3165T>C	p.Asn1055Asn	synonymous	Exon 17 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.3165T>C	p.Asn1055Asn	synonymous	Exon 17 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47772 AN: 151872 Hom.: 8277 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.272

GnomAD2 exomes AF: 0.256 AC: 64400 AN: 251404 AF XY: 0.252

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.0800

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.267 AC: 390877 AN: 1461748 Hom.: 54422 Cov.: 37 AF XY: 0.265 AC XY: 192727 AN XY: 727180

African (AFR) AF: 0.466 AC: 15597 AN: 33478

American (AMR) AF: 0.209 AC: 9353 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8740 AN: 26130

East Asian (EAS) AF: 0.0795 AC: 3155 AN: 39700

South Asian (SAS) AF: 0.222 AC: 19183 AN: 86258

European-Finnish (FIN) AF: 0.299 AC: 15992 AN: 53416

Middle Eastern (MID) AF: 0.230 AC: 1328 AN: 5766

European-Non Finnish (NFE) AF: 0.271 AC: 301609 AN: 1111886

Other (OTH) AF: 0.264 AC: 15920 AN: 60390

GnomAD4 genome AF: 0.315 AC: 47849 AN: 151990 Hom.: 8301 Cov.: 32 AF XY: 0.310 AC XY: 23040 AN XY: 74286

African (AFR) AF: 0.459 AC: 19011 AN: 41422

American (AMR) AF: 0.244 AC: 3736 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3468

East Asian (EAS) AF: 0.0790 AC: 409 AN: 5176

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4814

European-Finnish (FIN) AF: 0.289 AC: 3050 AN: 10560

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18392 AN: 67950

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.268 Hom.: 3387

Bravo AF: 0.318

Asia WGS AF: 0.206 AC: 717 AN: 3478

EpiCase AF: 0.256

EpiControl AF: 0.256

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Holoprosencephaly 11 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.022
DANN	Benign	0.31
PhyloP100		-1.9
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: rs564214; hg19: chr11-125851055; COSMIC: COSV54998321;