NM_001378964.1:c.2996-48G>T

Variant names:

• chr11-125981377-C-A
• rs3824922
• NM_001378964.1:c.2996-48G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.2996-48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,570,440 control chromosomes in the GnomAD database, including 2,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (262 hom., cov: 32)
  • Exomes 𝑓: 0.050 (2413 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.19
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-125981377-C-A is Benign according to our data. Variant chr11-125981377-C-A is described in ClinVar as Benign. ClinVar VariationId is 260790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.2996-48G>T		intron	N/A	NP_001365893.1
	CDON	NM_001243597.3		c.2996-48G>T		intron	N/A	NP_001230526.1
	CDON	NM_001441161.1		c.2996-48G>T		intron	N/A	NP_001428090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.2996-48G>T		intron	N/A	ENSP00000432901.2
	CDON	ENST00000392693.7	TSL:1	c.2996-48G>T		intron	N/A	ENSP00000376458.3
	CDON	ENST00000263577.11	TSL:1	c.2996-48G>T		intron	N/A	ENSP00000263577.7

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6870 AN: 149968 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0246

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0798

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.0496

GnomAD2 exomes AF: 0.0637 AC: 15087 AN: 236944 AF XY: 0.0606

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.00958

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.0338

Gnomad NFE exome AF: 0.0439

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0502 AC: 71245 AN: 1420354 Hom.: 2413 Cov.: 31 AF XY: 0.0504 AC XY: 35679 AN XY: 708100

African (AFR) AF: 0.0135 AC: 441 AN: 32678

American (AMR) AF: 0.140 AC: 6181 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.00858 AC: 221 AN: 25752

East Asian (EAS) AF: 0.109 AC: 4313 AN: 39448

South Asian (SAS) AF: 0.0727 AC: 6178 AN: 85004

European-Finnish (FIN) AF: 0.0334 AC: 1369 AN: 41030

Middle Eastern (MID) AF: 0.0300 AC: 169 AN: 5640

European-Non Finnish (NFE) AF: 0.0453 AC: 49302 AN: 1087294

Other (OTH) AF: 0.0518 AC: 3071 AN: 59282

GnomAD4 genome AF: 0.0457 AC: 6865 AN: 150086 Hom.: 262 Cov.: 32 AF XY: 0.0482 AC XY: 3529 AN XY: 73246

African (AFR) AF: 0.0169 AC: 697 AN: 41150

American (AMR) AF: 0.126 AC: 1896 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3456

East Asian (EAS) AF: 0.103 AC: 529 AN: 5138

South Asian (SAS) AF: 0.0788 AC: 376 AN: 4772

European-Finnish (FIN) AF: 0.0302 AC: 306 AN: 10132

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0430 AC: 2883 AN: 67092

Other (OTH) AF: 0.0515 AC: 106 AN: 2060

Alfa AF: 0.0130 Hom.: 0

Bravo AF: 0.0487

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		1.2
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: rs3824922; hg19: chr11-125851272; COSMIC: COSV54996117;