rs73410959

Positions:

chr15-42736428-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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:

CDAN1 (HGNC:):

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=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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	2/28	ENST00000356231.4	NP_612486.2	Q8IWY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	2/28	1	NM_138477.4	ENSP00000348564.3		Q8IWY9-2
CDAN1	ENST00000643434.1 linkuse as main transcript	n.91-347C>T		intron_variant				ENSP00000494699.1		A0A2R8Y5C2

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

GnomAD3 exomes

AF:

0.0250

AC:

5473

AN:

219152

Hom.:

289

AF XY:

0.0233

AC XY:

2808

AN XY:

120746

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 SAS exome

AF:

0.0285

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

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.0323

Gnomad4 EAS exome

AF:

0.0510

Gnomad4 SAS exome

AF:

0.0290

Gnomad4 FIN exome

AF:

0.000340

Gnomad4 NFE exome

AF:

0.00420

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0580

AC:

8832

AN:

152152

Hom.:

658

Cov.:

AF XY:

0.0563

AC XY:

4186

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.0218

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.0581

Gnomad4 SAS

AF:

0.0271

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00510

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0298

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

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	This variant is associated with the following publications: (PMID: 29146883) -
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

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

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

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

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