16-57436730-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020313.4(CIAPIN1):c.313A>G(p.Asn105Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: CIAPIN1 NM_020313.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0350

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 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=0.022553086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIAPIN1	NM_020313.4	c.313A>G	p.Asn105Asp	missense_variant, splice_region_variant	4/9	ENST00000394391.9
CIAPIN1	NM_001308347.2	c.274A>G	p.Asn92Asp	missense_variant, splice_region_variant	4/9
CIAPIN1	NM_001308358.2	c.313A>G	p.Asn105Asp	missense_variant, splice_region_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIAPIN1	ENST00000394391.9	c.313A>G	p.Asn105Asp	missense_variant, splice_region_variant	4/9	1	NM_020313.4	P1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000257 AC: 64 AN: 249166 Hom.: 0 AF XY: 0.000237 AC XY: 32 AN XY: 135228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000353

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000141 AC: 206 AN: 1460940 Hom.: 0 Cov.: 29 AF XY: 0.000147 AC XY: 107 AN XY: 726828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.000613

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74492

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000713 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000487 AC: 4

ExAC AF: 0.000190 AC: 23

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.313A>G (p.N105D) alteration is located in exon 4 (coding exon 3) of the CIAPIN1 gene. This alteration results from a A to G substitution at nucleotide position 313, causing the asparagine (N) at amino acid position 105 to be replaced by an aspartic acid (D). 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	0.066
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.061	T;.;.;.;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.70	T;T;.;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.023	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.
MutationTaster	Benign	0.86	D;D;D;D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.62	N;N;N;N;N;N
REVEL	Benign	0.027
Sift	Benign	0.20	T;T;T;T;T;T
Sift4G	Benign	0.58	T;T;T;T;T;T
Polyphen		0.0010	B;B;.;.;.;.
Vest4		0.20
MVP		0.23
MPC		0.24
ClinPred		0.027	T
GERP RS		1.4
Varity_R		0.14
gMVP		0.30

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

Other links and lift over

dbSNP: rs200237174; hg19: chr16-57470642;