Variant rs76599133 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138477.4(CDAN1):c.816C>A(p.Thr272=) 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

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 -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 id 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/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4 linkuse as main transcript	c.816C>A	p.Thr272=	synonymous_variant	4/28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4 linkuse as main transcript	c.816C>A	p.Thr272=	synonymous_variant	4/28	1	NM_138477.4	ENSP00000348564	P1	Q8IWY9-2
CDAN1	ENST00000643434.1 linkuse as main transcript	c.*115C>A		3_prime_UTR_variant, NMD_transcript_variant	3/25			ENSP00000494699

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

GnomAD3 exomes

AF:

0.0299

AC:

7491

AN:

250348

Hom.:

484

AF XY:

0.0271

AC XY:

3679

AN XY:

135738

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 SAS exome

AF:

0.0354

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

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.00520

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0345

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00270

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0603

AC:

9172

AN:

152208

Hom.:

776

Cov.:

AF XY:

0.0588

AC XY:

4375

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.0253

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.0456

Alfa

AF:

0.0331

Hom.:

134

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 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 13, 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 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.0

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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