Genetic Variant CDIN1:p.Pro33Leu (chr15-36579958-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001321759.2(CDIN1):c.98C>T(p.Pro33Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00045 in 1,612,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

CDIN1
NM_001321759.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.31

Publications

2 publications found

Variant links:

Genes affected

CDIN1 (HGNC:26929): (CDAN1 interacting nuclease 1) This gene encodes a protein with two predicted helix-turn-helix domains. Mutations in this gene were found in families with congenital dyserythropoietic anemia type Ib. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

CDIN1 Gene-Disease associations (from GenCC):

congenital dyserythropoietic anemia type type 1B
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital dyserythropoietic anemia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CDIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13563484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321759.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDIN1	NM_001321759.2	MANE Select	c.98C>T	p.Pro33Leu	missense	Exon 1 of 11	NP_001308688.1	Q9Y2V0-1
CDIN1	NM_001321761.2		c.98C>T	p.Pro33Leu	missense	Exon 1 of 11	NP_001308690.1	H3BS01
CDIN1	NM_001290233.2		c.98C>T	p.Pro33Leu	missense	Exon 1 of 11	NP_001277162.1	A0A2R8YD89

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.98C>T	p.Pro33Leu	missense	Exon 1 of 11	ENSP00000455397.1	Q9Y2V0-1
CDIN1	ENST00000437989.6	TSL:1	c.98C>T	p.Pro33Leu	missense	Exon 1 of 12	ENSP00000401362.2	Q9Y2V0-1
CDIN1	ENST00000569302.6	TSL:5	c.98C>T	p.Pro33Leu	missense	Exon 1 of 11	ENSP00000456477.1	H3BS01

Frequencies

GnomAD3 genomes

AF:

0.000282

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000234

AC:

AN:

243190

AF XY:

0.000234

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000283

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000468

AC:

683

AN:

1460232

Hom.:

Cov.:

AF XY:

0.000475

AC XY:

345

AN XY:

726238

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33458

American (AMR)

AF:

0.0000449

AC:

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.000151

AC:

AN:

85810

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000558

AC:

620

AN:

1111244

Other (OTH)

AF:

0.000431

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000282

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000290

Hom.:

Bravo

AF:

0.000268

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000319

AC:

ESP6500EA

AF:

0.000419

AC:

ExAC

AF:

0.000257

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital dyserythropoietic anemia type type 1B (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.042

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.1

PhyloP100

4.3

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.22

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.45

MVP

0.55

MPC

0.58

ClinPred

0.59

GERP RS

5.3

PromoterAI

0.0079

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.67

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over