Variant 15-36645260-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001321759.2(CDIN1):c.185C>T(p.Ser62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,553,158 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S62S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 13 hom. )

Consequence

CDIN1
NM_001321759.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.16

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004472494).

BP6

Variant 15-36645260-C-T is Benign according to our data. Variant chr15-36645260-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDIN1	NM_001321759.2 linkuse as main transcript	c.185C>T	p.Ser62Leu	missense_variant	3/11	ENST00000566621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDIN1	ENST00000566621.6 linkuse as main transcript	c.185C>T	p.Ser62Leu	missense_variant	3/11	5	NM_001321759.2	P1	Q9Y2V0-1
	ENST00000565366.1 linkuse as main transcript	n.122-3300G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

350

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00409

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00214

AC:

344

AN:

160848

Hom.:

AF XY:

0.00197

AC XY:

168

AN XY:

85474

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.000914

Gnomad ASJ exome

AF:

0.00137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00425

Gnomad OTH exome

AF:

0.00111

GnomAD4 exome

AF:

0.00402

AC:

5631

AN:

1401002

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

2700

AN XY:

691260

show subpopulations

Gnomad4 AFR exome

AF:

0.000820

Gnomad4 AMR exome

AF:

0.000803

Gnomad4 ASJ exome

AF:

0.00185

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.00160

Gnomad4 NFE exome

AF:

0.00491

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00230

AC:

350

AN:

152156

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000988

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00114

Gnomad4 NFE

AF:

0.00409

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00227

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00386

AC:

ExAC

AF:

0.00105

AC:

108

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 23, 2022	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function -

CDIN1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0063

T;.;.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.80

.;T;T;.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0045

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

N;.;N;.;.;N

REVEL

Benign

0.022

Sift

Benign

0.23

T;.;T;.;.;T

Sift4G

Benign

0.23

T;.;T;.;.;T

Polyphen

0.019

B;.;.;B;.;B

Vest4

0.15

MVP

0.14

MPC

0.12

ClinPred

0.00074

GERP RS

-0.34

Varity_R

0.050

gMVP

0.23

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