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 NM_032499.6(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
NM_032499.6 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:

Genome browser will be placed here

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032499.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDIN1	NM_001321759.2	MANE Select	c.217C>A	p.Leu73Met	missense	Exon 4 of 11	NP_001308688.1
CDIN1	NM_001290232.2		c.-78C>A		5_prime_UTR_premature_start_codon_gain	Exon 4 of 11	NP_001277161.1
CDIN1	NM_001321756.2		c.-78C>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	NP_001308685.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDIN1	ENST00000562877.5	TSL:1	c.-78C>A		5_prime_UTR_premature_start_codon_gain	Exon 4 of 11	ENSP00000457854.1
CDIN1	ENST00000567389.5	TSL:1	c.-78C>A		5_prime_UTR_premature_start_codon_gain	Exon 5 of 12	ENSP00000456736.1
CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.217C>A	p.Leu73Met	missense	Exon 4 of 11	ENSP00000455397.1

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 v4.9

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

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Benign

0.012

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

PhyloP100

3.7

PROVEAN

Benign

-0.40

REVEL

Benign

0.11

Sift

Benign

0.052

Sift4G

Benign

0.076

Polyphen

0.99

Vest4

0.34

MutPred

0.27

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over