rs73410959

Variant names:

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.443C>T(p.Ala148Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,600,120 control chromosomes in the GnomAD database, including 1,497 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A148T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.058 ( 658 hom., cov: 32)

Exomes 𝑓: 0.013 ( 839 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.12

Publications

7 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=0.0011544526).

BP6

Variant 15-42736428-G-A is Benign according to our data. Variant chr15-42736428-G-A is described in ClinVar as Benign. ClinVar VariationId is 262377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138477.4. 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
	CDAN1	NM_138477.4	MANE Select	c.443C>T	p.Ala148Val	missense	Exon 2 of 28	NP_612486.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.443C>T	p.Ala148Val	missense	Exon 2 of 28	ENSP00000348564.3
CDAN1	ENST00000643434.1		n.91-347C>T		intron	N/A	ENSP00000494699.1
CDAN1	ENST00000563260.1	TSL:3	c.*134C>T		downstream_gene	N/A	ENSP00000455536.1

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8812

AN:

152036

Hom.:

656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0218

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.0581

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.0426

GnomAD2 exomes

AF:

0.0250

AC:

5473

AN:

219152

AF XY:

0.0233

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.00979

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.0654

Gnomad FIN exome

AF:

0.000404

Gnomad NFE exome

AF:

0.00521

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0126

AC:

18300

AN:

1447968

Hom.:

839

Cov.:

AF XY:

0.0127

AC XY:

9110

AN XY:

719152

show subpopulations

African (AFR)

AF:

0.195

AC:

6452

AN:

33156

American (AMR)

AF:

0.0114

AC:

497

AN:

43504

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

835

AN:

25838

East Asian (EAS)

AF:

0.0510

AC:

1997

AN:

39160

South Asian (SAS)

AF:

0.0290

AC:

2471

AN:

85138

European-Finnish (FIN)

AF:

0.000340

AC:

AN:

49964

Middle Eastern (MID)

AF:

0.0179

AC:

102

AN:

5690

European-Non Finnish (NFE)

AF:

0.00420

AC:

4646

AN:

1105828

Other (OTH)

AF:

0.0215

AC:

1283

AN:

59690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

883

1767

2650

3534

4417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.0580

AC:

8832

AN:

152152

Hom.:

658

Cov.:

AF XY:

0.0563

AC XY:

4186

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.181

AC:

7519

AN:

41516

American (AMR)

AF:

0.0218

AC:

333

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3470

East Asian (EAS)

AF:

0.0581

AC:

299

AN:

5146

South Asian (SAS)

AF:

0.0271

AC:

131

AN:

4826

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00510

AC:

347

AN:

67978

Other (OTH)

AF:

0.0426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

369

738

1108

1477

1846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0345

Hom.:

Bravo

AF:

0.0648

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.149

AC:

622

ESP6500EA

AF:

0.00480

AC:

ExAC

AF:

0.0260

AC:

3103

Asia WGS

AF:

0.0480

AC:

167

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Anemia, congenital dyserythropoietic, type 1a (1)

Congenital dyserythropoietic anemia, type I (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.1

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.79

REVEL

Benign

0.17

Sift

Benign

0.23

Sift4G

Uncertain

0.035

Polyphen

0.091

Vest4

0.038

MPC

0.96

ClinPred

0.0022

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.54

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over