NM_138477.4:c.3474A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138477.4(CDAN1):c.3474A>C(p.Leu1158Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,613,572 control chromosomes in the GnomAD database, including 75,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 18329 hom., cov: 32)

Exomes 𝑓: 0.26 ( 57421 hom. )

Consequence

CDAN1
NM_138477.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.474

Publications

31 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 15-42725228-T-G is Benign according to our data. Variant chr15-42725228-T-G is described in ClinVar as Benign. ClinVar VariationId is 262376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.474 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.3474A>C	p.Leu1158Leu	synonymous_variant	Exon 27 of 28	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.3474A>C	p.Leu1158Leu	synonymous_variant	Exon 27 of 28	1	NM_138477.4	ENSP00000348564.3		Q8IWY9-2

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61627

AN:

151974

Hom.:

18268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.356

GnomAD2 exomes

AF:

0.289

AC:

72666

AN:

251402

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.850

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.256

AC:

374211

AN:

1461480

Hom.:

57421

Cov.:

AF XY:

0.261

AC XY:

189605

AN XY:

727086

show subpopulations

African (AFR)

AF:

0.867

AC:

29020

AN:

33480

American (AMR)

AF:

0.156

AC:

6989

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8370

AN:

26136

East Asian (EAS)

AF:

0.248

AC:

9859

AN:

39698

South Asian (SAS)

AF:

0.439

AC:

37825

AN:

86248

European-Finnish (FIN)

AF:

0.253

AC:

13526

AN:

53414

Middle Eastern (MID)

AF:

0.309

AC:

1785

AN:

5768

European-Non Finnish (NFE)

AF:

0.224

AC:

249268

AN:

1111636

Other (OTH)

AF:

0.291

AC:

17569

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15532

31065

46597

62130

77662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8926

17852

26778

35704

44630

<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:

61743

AN:

152092

Hom.:

18329

Cov.:

AF XY:

0.402

AC XY:

29905

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.840

AC:

34874

AN:

41500

American (AMR)

AF:

0.220

AC:

3368

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1113

AN:

3464

East Asian (EAS)

AF:

0.251

AC:

1297

AN:

5160

South Asian (SAS)

AF:

0.427

AC:

2057

AN:

4822

European-Finnish (FIN)

AF:

0.255

AC:

2696

AN:

10576

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15426

AN:

67960

Other (OTH)

AF:

0.352

AC:

741

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1341

2682

4023

5364

6705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.265

Hom.:

10585

Bravo

AF:

0.418

Asia WGS

AF:

0.359

AC:

1249

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 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 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

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.0

(source)

DANN

Benign

0.72

PhyloP100

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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