16-57439277-G-A

Variant names:

• chr16-57439277-G-A
• rs368064049
• NM_020313.4:c.215C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020313.4(CIAPIN1):​c.215C>T​(p.Thr72Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: CIAPIN1 NM_020313.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08897972).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020313.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIAPIN1	NM_020313.4	MANE Select	c.215C>T	p.Thr72Ile	missense	Exon 3 of 9	NP_064709.2	Q6FI81-1
	CIAPIN1	NM_001308347.2		c.176C>T	p.Thr59Ile	missense	Exon 3 of 9	NP_001295276.1	Q6FI81-3
	CIAPIN1	NM_001308358.2		c.215C>T	p.Thr72Ile	missense	Exon 3 of 8	NP_001295287.1	H3BT65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIAPIN1	ENST00000394391.9	TSL:1 MANE Select	c.215C>T	p.Thr72Ile	missense	Exon 3 of 9	ENSP00000377914.4	Q6FI81-1
	CIAPIN1	ENST00000567518.5	TSL:1	c.176C>T	p.Thr59Ile	missense	Exon 3 of 9	ENSP00000456114.1	Q6FI81-3
	CIAPIN1	ENST00000939128.1		c.176C>T	p.Thr59Ile	missense	Exon 3 of 9	ENSP00000609187.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249554 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000821 AC: 12 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727236

African (AFR) AF: 0.000269 AC: 9 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74466

African (AFR) AF: 0.000361 AC: 15 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.000265 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000579 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Benign	0.066	T
Sift4G	Benign	0.064	T
Polyphen		0.73	P
Vest4		0.34
MVP		0.53
MPC		0.28
ClinPred		0.17	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.22
gMVP		0.39
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs368064049; hg19: chr16-57473189;