rs861818

chr22-21697294-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014337.4(PPIL2):c.*1804G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 361,046 control chromosomes in the GnomAD database, including 5,092 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 0.18 (2552 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2540 hom.)
• Consequence: PPIL2 NM_014337.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIL2	NM_014337.4	c.*1804G>T		3_prime_UTR_variant	20/20	ENST00000398831.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIL2	ENST00000398831.8	c.*1804G>T		3_prime_UTR_variant	20/20	1	NM_014337.4	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26692 AN: 152008 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.144 AC: 30141 AN: 208920 Hom.: 2540 Cov.: 0 AF XY: 0.140 AC XY: 15434 AN XY: 110372

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.0897

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.176 AC: 26724 AN: 152126 Hom.: 2552 Cov.: 32 AF XY: 0.174 AC XY: 12916 AN XY: 74374

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.179

Alfa AF: 0.168 Hom.: 2287

Bravo AF: 0.176

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.3
Dann	Benign	0.74
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

Other links and lift over

dbSNP: rs861818; hg19: chr22-22051583;