rs76599133

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.816C>A(p.Thr272Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,614,048 control chromosomes in the GnomAD database, including 1,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 776 hom., cov: 32)

Exomes 𝑓: 0.013 ( 1008 hom. )

Consequence

CDAN1
NM_138477.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.228

Publications

6 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=-0.63).

BP6

Variant 15-42735637-G-T is Benign according to our data. Variant chr15-42735637-G-T is described in ClinVar as Benign. ClinVar VariationId is 262380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.228 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.816C>A	p.Thr272Thr	synonymous_variant	Exon 4 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CDAN1	ENST00000356231.4 link	c.816C>A	p.Thr272Thr	synonymous_variant	Exon 4 of 28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000643434.1 link	n.*115C>A		non_coding_transcript_exon_variant	Exon 3 of 25			ENSP00000494699.1
CDAN1	ENST00000643434.1 link	n.*115C>A		3_prime_UTR_variant	Exon 3 of 25			ENSP00000494699.1

Frequencies

GnomAD3 genomes

AF:

0.0601

AC:

9137

AN:

152092

Hom.:

769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0365

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.0465

GnomAD2 exomes

AF:

0.0299

AC:

7491

AN:

250348

AF XY:

0.0271

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.00578

Gnomad EAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00343

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0131

AC:

19091

AN:

1461840

Hom.:

1008

Cov.:

AF XY:

0.0131

AC XY:

9529

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.191

AC:

6402

AN:

33480

American (AMR)

AF:

0.0165

AC:

738

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00520

AC:

136

AN:

26136

East Asian (EAS)

AF:

0.104

AC:

4130

AN:

39700

South Asian (SAS)

AF:

0.0345

AC:

2973

AN:

86258

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.0231

AC:

133

AN:

5766

European-Non Finnish (NFE)

AF:

0.00270

AC:

3003

AN:

1111992

Other (OTH)

AF:

0.0258

AC:

1560

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1202

2403

3605

4806

6008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.0603

AC:

9172

AN:

152208

Hom.:

776

Cov.:

AF XY:

0.0588

AC XY:

4375

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.184

AC:

7637

AN:

41484

American (AMR)

AF:

0.0253

AC:

387

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.122

AC:

629

AN:

5176

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4824

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00315

AC:

214

AN:

68016

Other (OTH)

AF:

0.0456

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

391

782

1172

1563

1954

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:

0.0322

Hom.:

187

Bravo

AF:

0.0670

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

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 15, 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

-0.63

CADD

Benign

6.0

(source)

DANN

Benign

0.64

PhyloP100

0.23

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