Genetic Variant CIAPIN1:p.Val143Ile (chr16-57434173-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020313.4(CIAPIN1):c.427G>A(p.Val143Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CIAPIN1
NM_020313.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

CIAPIN1 (HGNC:28050): (cytokine induced apoptosis inhibitor 1) CIAPIN1 is a cytokine-induced inhibitor of apoptosis with no relation to apoptosis regulatory molecules of the BCL2 (MIM 151430) or CASP (see MIM 147678) families. Expression of CIAPIN1 is dependent on growth factor stimulation (Shibayama et al., 2004 [PubMed 14970183]).[supplied by OMIM, Mar 2008]

CIAPIN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06620243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAPIN1	NM_020313.4 link	c.427G>A	p.Val143Ile	missense_variant	Exon 5 of 9	ENST00000394391.9	NP_064709.2	Q6FI81-1
CIAPIN1	NM_001308347.2 link	c.388G>A	p.Val130Ile	missense_variant	Exon 5 of 9		NP_001295276.1	Q6FI81-3
CIAPIN1	NM_001308358.2 link	c.427G>A	p.Val143Ile	missense_variant	Exon 5 of 8		NP_001295287.1	Q6FI81H3BT65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAPIN1	ENST00000394391.9 link	c.427G>A	p.Val143Ile	missense_variant	Exon 5 of 9	1	NM_020313.4	ENSP00000377914.4		Q6FI81-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249568

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727212

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.427G>A (p.V143I) alteration is located in exon 5 (coding exon 4) of the CIAPIN1 gene. This alteration results from a G to A substitution at nucleotide position 427, causing the valine (V) at amino acid position 143 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.023

T;.;T;.;.;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.79

T;T;T;.;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.066

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

0.090

N;N;N;N;N;N

REVEL

Benign

0.027

Sift

Benign

0.20

T;T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T;T

Polyphen

0.0010

B;B;.;.;.;.

Vest4

0.12

MutPred

0.44

Gain of glycosylation at S142 (P = 0.2007);.;.;Gain of glycosylation at S142 (P = 0.2007);Gain of glycosylation at S142 (P = 0.2007);Gain of glycosylation at S142 (P = 0.2007);

MVP

0.11

MPC

0.17

ClinPred

0.058

GERP RS

2.2

Varity_R

0.063

gMVP

0.62

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