rs3740904

Variant names:

• chr11-125978366-C-T
• rs3740904
• NM_001378964.1:c.3294G>A
• CDON p.Thr1098Thr

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001378964.1(CDON):​c.3294G>A​(p.Thr1098Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,598,876 control chromosomes in the GnomAD database, including 109,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10640 hom., cov: 32)
  • Exomes 𝑓: 0.37 (99290 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.325
• Publications: 22 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, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 11-125978366-C-T is Benign according to our data. Variant chr11-125978366-C-T is described in ClinVar as Benign. ClinVar VariationId is 260793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.325 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 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.3294G>A	p.Thr1098Thr	synonymous	Exon 18 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.3294G>A	p.Thr1098Thr	synonymous	Exon 18 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.3294G>A	p.Thr1098Thr	synonymous	Exon 18 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.3294G>A	p.Thr1098Thr	synonymous	Exon 18 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.3294G>A	p.Thr1098Thr	synonymous	Exon 18 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.3294G>A	p.Thr1098Thr	synonymous	Exon 18 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56533 AN: 151750 Hom.: 10624 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.384 AC: 93281 AN: 243128 AF XY: 0.383

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.384

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.368 AC: 532225 AN: 1447008 Hom.: 99290 Cov.: 30 AF XY: 0.369 AC XY: 265159 AN XY: 719560

African (AFR) AF: 0.354 AC: 11759 AN: 33258

American (AMR) AF: 0.440 AC: 19355 AN: 44014

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 9222 AN: 26030

East Asian (EAS) AF: 0.384 AC: 15186 AN: 39576

South Asian (SAS) AF: 0.401 AC: 33937 AN: 84622

European-Finnish (FIN) AF: 0.409 AC: 21722 AN: 53110

Middle Eastern (MID) AF: 0.351 AC: 2010 AN: 5734

European-Non Finnish (NFE) AF: 0.360 AC: 396375 AN: 1100754

Other (OTH) AF: 0.378 AC: 22659 AN: 59910

GnomAD4 genome AF: 0.373 AC: 56589 AN: 151868 Hom.: 10640 Cov.: 32 AF XY: 0.378 AC XY: 28048 AN XY: 74202

African (AFR) AF: 0.352 AC: 14589 AN: 41400

American (AMR) AF: 0.428 AC: 6526 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1212 AN: 3460

East Asian (EAS) AF: 0.389 AC: 2009 AN: 5158

South Asian (SAS) AF: 0.403 AC: 1938 AN: 4806

European-Finnish (FIN) AF: 0.427 AC: 4497 AN: 10542

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24658 AN: 67934

Other (OTH) AF: 0.361 AC: 762 AN: 2110

Alfa AF: 0.364 Hom.: 31328

Bravo AF: 0.369

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.72
DANN	Benign	0.66
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3740904;

hg19: chr11-125848261;

COSMIC: COSV54996106;