rs4265781

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 21751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42736551-T-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.320A>T	p.Gln107Leu	missense_variant	2/28	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDAN1	ENST00000356231.4 link	c.320A>T	p.Gln107Leu	missense_variant	2/28	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000643434.1 link	n.90+462A>T		intron_variant				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

GnomAD3 exomes

AF:

0.271

AC:

24342

AN:

89986

Hom.:

3963

AF XY:

0.288

AC XY:

14682

AN XY:

50950

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 SAS exome

AF:

0.433

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

Gnomad4 AFR exome

AF:

0.870

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.319

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.224

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.406

AC:

61446

AN:

151428

Hom.:

18255

Cov.:

AF XY:

0.402

AC XY:

29772

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.840

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.422

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.352

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital dyserythropoietic anemia, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over