rs4265781

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138477.4(CDAN1):c.320A>T(p.Gln107Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,483,802 control chromosomes in the GnomAD database, including 68,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 18255 hom., cov: 31)

Exomes 𝑓: 0.25 ( 50526 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.547

Publications

27 publications found

Variant links:

Genes affected

CDAN1 (HGNC:1713): (codanin 1) This gene encodes a protein that appears to play a role in nuclear envelope integrity, possibly related to microtubule attachments. Mutations in this gene cause congenital dyserythropoietic anemia type I, a disease resulting in morphological and functional abnormalities of erythropoiesis. [provided by RefSeq, Jul 2009]

CDAN1 Gene-Disease associations (from GenCC):

anemia, congenital dyserythropoietic, type 1a
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital dyserythropoietic anemia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital dyserythropoietic anemia
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

CDAN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=7.0060685E-7).

BP6

Variant 15-42736551-T-A is Benign according to our data. Variant chr15-42736551-T-A is described in ClinVar as Benign. ClinVar VariationId is 21751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.320A>T	p.Gln107Leu	missense_variant	Exon 2 of 28	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDAN1	ENST00000356231.4 link	c.320A>T	p.Gln107Leu	missense_variant	Exon 2 of 28	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000643434.1 link	n.90+462A>T		intron_variant	Intron 1 of 24			ENSP00000494699.1	A0A2R8Y5C2
CDAN1	ENST00000563260.1 link	c.*11A>T		downstream_gene_variant		3		ENSP00000455536.1	H3BPZ6

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61337

AN:

151320

Hom.:

18197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.839

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.356

GnomAD2 exomes

AF:

0.271

AC:

24342

AN:

89986

AF XY:

0.288

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.253

AC:

336969

AN:

1332374

Hom.:

50526

Cov.:

AF XY:

0.258

AC XY:

169231

AN XY:

657142

show subpopulations

African (AFR)

AF:

0.870

AC:

23232

AN:

26708

American (AMR)

AF:

0.160

AC:

4552

AN:

28508

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

7409

AN:

23234

East Asian (EAS)

AF:

0.243

AC:

7181

AN:

29496

South Asian (SAS)

AF:

0.435

AC:

32000

AN:

73584

European-Finnish (FIN)

AF:

0.254

AC:

9614

AN:

37924

Middle Eastern (MID)

AF:

0.317

AC:

1388

AN:

4384

European-Non Finnish (NFE)

AF:

0.224

AC:

235476

AN:

1053510

Other (OTH)

AF:

0.293

AC:

16117

AN:

55026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

13816

27631

41447

55262

69078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8582

17164

25746

34328

42910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.406

AC:

61446

AN:

151428

Hom.:

18255

Cov.:

AF XY:

0.402

AC XY:

29772

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.840

AC:

34790

AN:

41426

American (AMR)

AF:

0.219

AC:

3333

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1113

AN:

3468

East Asian (EAS)

AF:

0.252

AC:

1273

AN:

5060

South Asian (SAS)

AF:

0.422

AC:

2030

AN:

4814

European-Finnish (FIN)

AF:

0.255

AC:

2660

AN:

10434

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.227

AC:

15336

AN:

67690

Other (OTH)

AF:

0.352

AC:

739

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1286

2571

3857

5142

6428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.211

Hom.:

840

Bravo

AF:

0.417

TwinsUK

AF:

0.215

AC:

798

ALSPAC

AF:

0.223

AC:

859

ExAC

AF:

0.294

AC:

4881

Asia WGS

AF:

0.352

AC:

1210

AN:

3440

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Congenital dyserythropoietic anemia, type I

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Anemia, congenital dyserythropoietic, type 1a

Benign:1

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.3

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.050

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.11

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

PhyloP100

-0.55

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.12

REVEL

Benign

0.26

Sift

Benign

0.34

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.023

MPC

0.83

ClinPred

0.0063

GERP RS

-1.2

Varity_R

0.049

gMVP

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over