dbSNP rs3784678: CDIN1:c.-78C>A (chr15-36654102-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000562877.5(CDIN1):c.-78C>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000154 in 1,423,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CDIN1
ENST00000562877.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70

Publications

36 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:

ENSG00000261191 (HGNC:):

ENSG00000261191 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35504982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIN1	NM_001321759.2 link	c.217C>A	p.Leu73Met	missense_variant	Exon 4 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.217C>A	p.Leu73Met	missense_variant	Exon 4 of 11	5	NM_001321759.2	ENSP00000455397.1		Q9Y2V0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1423980

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

704378

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

33014

American (AMR)

AF:

0.00

AC:

AN:

39430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25576

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38448

South Asian (SAS)

AF:

0.00

AC:

AN:

81152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000183

AC:

AN:

1090506

Other (OTH)

AF:

0.00

AC:

AN:

59012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

11605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

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

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

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

M_CAP

Benign

0.012

MetaRNN

Benign

0.36

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

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

M;.;.;.;M;.;M

PhyloP100

3.7

PROVEAN

Benign

-0.40

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

REVEL

Benign

0.11

Sift

Benign

0.052

T;.;D;D;.;.;T

Sift4G

Benign

0.076

T;.;D;T;.;.;T

Polyphen

0.99

D;.;.;.;D;.;D

Vest4

0.34

MutPred

0.27

Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);.;Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);

MVP

0.35

MPC

0.56

ClinPred

0.90

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.28

Mutation Taster

=200/100

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over