rs12905385

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138477.4(CDAN1):c.2408-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.204 in 1,613,582 control chromosomes in the GnomAD database, including 37,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5076 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31974 hom. )

Consequence

CDAN1
NM_138477.4 splice_region, intron

Scores

Splicing: ADA: 0.003605

Clinical Significance

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

Conservation

PhyloP100: 6.03

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 (BayesDel_noAF=-0.47).

BP6

Variant 15-42729365-G-A is Benign according to our data. Variant chr15-42729365-G-A is described in ClinVar as [Benign]. Clinvar id is 262371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42729365-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4 link	c.2408-3C>T		splice_region_variant, intron_variant	Intron 17 of 27	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDAN1	ENST00000356231.4 link	c.2408-3C>T	splice_region_variant, intron_variant	Intron 17 of 27	1	NM_138477.4	ENSP00000348564.3	Q8IWY9-2
CDAN1	ENST00000562465.5 link	n.401-3C>T	splice_region_variant, intron_variant	Intron 4 of 14	1		ENSP00000454246.1	H3BM60
CDAN1	ENST00000643434.1 link	n.*1586-3C>T	splice_region_variant, intron_variant	Intron 15 of 24			ENSP00000494699.1	A0A2R8Y5C2

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36270

AN:

152010

Hom.:

5075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.0545

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.221

GnomAD3 exomes

AF:

0.201

AC:

50428

AN:

250652

Hom.:

6153

AF XY:

0.209

AC XY:

28324

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.0934

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0562

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.200

AC:

292280

AN:

1461454

Hom.:

31974

Cov.:

AF XY:

0.204

AC XY:

148518

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.0992

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.0699

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.239

AC:

36292

AN:

152128

Hom.:

5076

Cov.:

AF XY:

0.239

AC XY:

17759

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.0548

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.197

Hom.:

4149

Bravo

AF:

0.234

Asia WGS

AF:

0.194

AC:

674

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.189

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 12, 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

-0.47

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0036

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.020

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