Genetic Variant CIAPIN1:c.-56+16G>T (chr16-57447326-C-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_020313.4(CIAPIN1):c.-56+16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 454,172 control chromosomes in the GnomAD database, including 1,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 863 hom., cov: 32)

Exomes 𝑓: 0.039 ( 378 hom. )

Consequence

CIAPIN1
NM_020313.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60

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:

COQ9 (HGNC:25302): (coenzyme Q9) This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.[provided by RefSeq, Sep 2010]

COQ9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 16-57447326-C-A is Benign according to our data. Variant chr16-57447326-C-A is described in ClinVar as [Benign]. Clinvar id is 1229725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CIAPIN1	NM_020313.4 link	c.-56+16G>T	intron_variant	Intron 1 of 8	ENST00000394391.9	NP_064709.2	Q6FI81-1
CIAPIN1	NM_001308347.2 link	c.-56+16G>T	intron_variant	Intron 1 of 8		NP_001295276.1	Q6FI81-3
CIAPIN1	NM_001308358.2 link	c.-56+16G>T	intron_variant	Intron 1 of 7		NP_001295287.1	Q6FI81H3BT65
COQ9	NM_020312.4 link	c.-180C>A	upstream_gene_variant		ENST00000262507.11	NP_064708.1	O75208-1A0A024R6U3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAPIN1	ENST00000394391.9 link	c.-56+16G>T		intron_variant	Intron 1 of 8	1	NM_020313.4	ENSP00000377914.4		Q6FI81-1
COQ9	ENST00000262507.11 link	c.-180C>A		upstream_gene_variant		1	NM_020312.4	ENSP00000262507.5		O75208-1

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12044

AN:

151442

Hom.:

863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0534

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.00627

Gnomad SAS

AF:

0.0719

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0766

GnomAD4 exome

AF:

0.0393

AC:

11896

AN:

302612

Hom.:

378

Cov.:

AF XY:

0.0390

AC XY:

5938

AN XY:

152186

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0472

Gnomad4 ASJ exome

AF:

0.0655

Gnomad4 EAS exome

AF:

0.000737

Gnomad4 SAS exome

AF:

0.0791

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0357

Gnomad4 OTH exome

AF:

0.0599

GnomAD4 genome

AF:

0.0796

AC:

12063

AN:

151560

Hom.:

863

Cov.:

AF XY:

0.0783

AC XY:

5803

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.0532

Gnomad4 ASJ

AF:

0.0628

Gnomad4 EAS

AF:

0.00629

Gnomad4 SAS

AF:

0.0721

Gnomad4 FIN

AF:

0.0216

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.0758

Alfa

AF:

0.0339

Hom.:

Bravo

AF:

0.0869

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.0

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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