16-57430320-C-G

Variant names:

• chr16-57430320-C-G
• NM_020313.4:c.766G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020313.4(CIAPIN1):​c.766G>C​(p.Glu256Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIAPIN1 NM_020313.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.51

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37601236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAPIN1	NM_020313.4	c.766G>C	p.Glu256Gln	missense_variant	Exon 8 of 9	ENST00000394391.9	NP_064709.2
CIAPIN1	NM_001308347.2	c.727G>C	p.Glu243Gln	missense_variant	Exon 8 of 9		NP_001295276.1
CIAPIN1	NM_001308358.2	c.650G>C	p.Arg217Thr	missense_variant	Exon 7 of 8		NP_001295287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAPIN1	ENST00000394391.9	c.766G>C	p.Glu256Gln	missense_variant	Exon 8 of 9	1	NM_020313.4	ENSP00000377914.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.766G>C (p.E256Q) alteration is located in exon 8 (coding exon 7) of the CIAPIN1 gene. This alteration results from a G to C substitution at nucleotide position 766, causing the glutamic acid (E) at amino acid position 256 to be replaced by a glutamine (Q). 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	0.31
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	D;D;N
REVEL	Benign	0.25
Sift	Benign	0.046	D;D;T
Sift4G	Uncertain	0.037	D;D;T
Polyphen		1.0	D;D;.
Vest4		0.36
MutPred		0.47		Gain of MoRF binding (P = 0.0761);.;.;
MVP		0.29
MPC		0.45
ClinPred		0.95	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.41
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-57464232;