Genetic Variant CDIN1:p.Asp9Gly (chr15-36579886-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001321759.2(CDIN1):c.26A>G(p.Asp9Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000255 in 1,613,956 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

CDIN1
NM_001321759.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.12

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071234405).

BP6

Variant 15-36579886-A-G is Benign according to our data. Variant chr15-36579886-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1309945.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIN1	NM_001321759.2 link	c.26A>G	p.Asp9Gly	missense_variant	Exon 1 of 11	ENST00000566621.6	NP_001308688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDIN1	ENST00000566621.6 link	c.26A>G	p.Asp9Gly	missense_variant	Exon 1 of 11	5	NM_001321759.2	ENSP00000455397.1		Q9Y2V0-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152210

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:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000601

AC:

148

AN:

246160

Hom.:

AF XY:

0.000799

AC XY:

107

AN XY:

133974

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000263

AC:

385

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

289

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00404

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000177

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000440

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000319

AC:

ESP6500EA

AF:

0.000279

AC:

ExAC

AF:

0.000688

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 11, 2019

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.;.;.;T;.;T

Eigen

Benign

-0.048

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.70

.;T;T;T;.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0071

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;.;.;L;.;L

PROVEAN

Benign

-1.5

N;.;N;N;.;.;N

REVEL

Benign

0.059

Sift

Benign

0.14

T;.;T;T;.;.;T

Sift4G

Benign

0.36

T;.;T;T;.;.;T

Polyphen

0.0

B;.;.;.;B;.;B

Vest4

0.39

MVP

0.36

MPC

0.18

ClinPred

0.12

GERP RS

5.3

Varity_R

0.39

gMVP

0.54

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