22-21667716-G-A

Variant names:

• chr22-21667716-G-A
• rs1103229
• NM_014337.4:c.32+1585G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014337.4(PPIL2):​c.32+1585G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 150,342 control chromosomes in the GnomAD database, including 1,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1230 hom., cov: 30)
• Consequence: PPIL2 NM_014337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 9 publications found

Genes affected

PPIL2 (HGNC:9261): (peptidylprolyl isomerase like 2) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ENSG00000207751 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014337.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	NM_014337.4	MANE Select	c.32+1585G>A		intron	N/A	NP_055152.1
	PPIL2	NM_148176.3		c.32+1585G>A		intron	N/A	NP_680481.1
	PPIL2	NM_001317996.2		c.32+1585G>A		intron	N/A	NP_001304925.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.32+1585G>A		intron	N/A	ENSP00000381812.3
	PPIL2	ENST00000626352.2	TSL:1	c.32+1585G>A		intron	N/A	ENSP00000486725.1
	PPIL2	ENST00000335025.12	TSL:1	c.32+1585G>A		intron	N/A	ENSP00000334553.7

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17136 AN: 150276 Hom.: 1229 Cov.: 30

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.000783

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17139 AN: 150342 Hom.: 1230 Cov.: 30 AF XY: 0.111 AC XY: 8162 AN XY: 73234

African (AFR) AF: 0.0389 AC: 1588 AN: 40870

American (AMR) AF: 0.109 AC: 1647 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3458

East Asian (EAS) AF: 0.000785 AC: 4 AN: 5094

South Asian (SAS) AF: 0.0986 AC: 467 AN: 4736

European-Finnish (FIN) AF: 0.151 AC: 1522 AN: 10056

Middle Eastern (MID) AF: 0.133 AC: 38 AN: 286

European-Non Finnish (NFE) AF: 0.162 AC: 11001 AN: 67794

Other (OTH) AF: 0.129 AC: 269 AN: 2078

Alfa AF: 0.148 Hom.: 3016

Bravo AF: 0.108

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.25
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs1103229; hg19: chr22-22022005;