chr11-125960802-T-C

Variant names:

• chr11-125960802-T-C
• rs3737336
• NM_001378964.1:c.*140A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.*140A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.293 in 790,096 control chromosomes in the GnomAD database, including 35,027 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5477 hom., cov: 32)
  • Exomes 𝑓: 0.30 (29550 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.78
• Publications: 23 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 -16 ACMG points.

• BP6: Variant 11-125960802-T-C is Benign according to our data. Variant chr11-125960802-T-C is described in ClinVar as Benign. ClinVar VariationId is 303488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 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.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.*140A>G		3_prime_UTR	Exon 20 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.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38761 AN: 152022 Hom.: 5475 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.302 AC: 192349 AN: 637956 Hom.: 29550 Cov.: 8 AF XY: 0.304 AC XY: 103436 AN XY: 340620

African (AFR) AF: 0.122 AC: 2090 AN: 17094

American (AMR) AF: 0.278 AC: 10170 AN: 36590

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 5460 AN: 18388

East Asian (EAS) AF: 0.279 AC: 9894 AN: 35498

South Asian (SAS) AF: 0.316 AC: 19331 AN: 61178

European-Finnish (FIN) AF: 0.311 AC: 15581 AN: 50064

Middle Eastern (MID) AF: 0.256 AC: 614 AN: 2396

European-Non Finnish (NFE) AF: 0.312 AC: 119654 AN: 384004

Other (OTH) AF: 0.292 AC: 9555 AN: 32744

GnomAD4 genome AF: 0.255 AC: 38780 AN: 152140 Hom.: 5477 Cov.: 32 AF XY: 0.257 AC XY: 19095 AN XY: 74356

African (AFR) AF: 0.126 AC: 5246 AN: 41526

American (AMR) AF: 0.264 AC: 4037 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1467 AN: 5170

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3363 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21254 AN: 67980

Other (OTH) AF: 0.250 AC: 530 AN: 2116

Alfa AF: 0.299 Hom.: 19859

Bravo AF: 0.247

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Holoprosencephaly 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		4.8
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: rs3737336; hg19: chr11-125830697; COSMIC: COSV54997022; COSMIC: COSV54997022;