rs56046122

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.3450+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,614,006 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 631 hom., cov: 32)

Exomes 𝑓: 0.017 ( 916 hom. )

Consequence

CDAN1
NM_138477.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.02

Publications

4 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 (BayesDel_noAF=-0.96).

BP6

Variant 15-42725478-G-A is Benign according to our data. Variant chr15-42725478-G-A is described in ClinVar as Benign. ClinVar VariationId is 262375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.3450+11C>T		intron_variant	Intron 26 of 27	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4 link	c.3450+11C>T		intron_variant	Intron 26 of 27	1	NM_138477.4	ENSP00000348564.3		Q8IWY9-2

Frequencies

GnomAD3 genomes

AF:

0.0603

AC:

9171

AN:

152088

Hom.:

629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.0591

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0450

GnomAD2 exomes

AF:

0.0298

AC:

7480

AN:

251044

AF XY:

0.0282

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0335

Gnomad EAS exome

AF:

0.0661

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0173

AC:

25248

AN:

1461800

Hom.:

916

Cov.:

AF XY:

0.0178

AC XY:

12928

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.188

AC:

6292

AN:

33474

American (AMR)

AF:

0.0143

AC:

638

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0367

AC:

960

AN:

26136

East Asian (EAS)

AF:

0.0517

AC:

2052

AN:

39700

South Asian (SAS)

AF:

0.0444

AC:

3828

AN:

86256

European-Finnish (FIN)

AF:

0.00352

AC:

188

AN:

53396

Middle Eastern (MID)

AF:

0.0229

AC:

132

AN:

5768

European-Non Finnish (NFE)

AF:

0.00864

AC:

9602

AN:

1111956

Other (OTH)

AF:

0.0258

AC:

1556

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1418

2835

4253

5670

7088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0604

AC:

9192

AN:

152206

Hom.:

631

Cov.:

AF XY:

0.0587

AC XY:

4367

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.176

AC:

7311

AN:

41518

American (AMR)

AF:

0.0240

AC:

367

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3470

East Asian (EAS)

AF:

0.0592

AC:

306

AN:

5170

South Asian (SAS)

AF:

0.0429

AC:

207

AN:

4826

European-Finnish (FIN)

AF:

0.00396

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

702

AN:

68004

Other (OTH)

AF:

0.0445

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

392

784

1177

1569

1961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0343

Hom.:

488

Bravo

AF:

0.0662

Asia WGS

AF:

0.0510

AC:

178

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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 13, 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 08, 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

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.6

(source)

DANN

Benign

0.46

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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