22-21694573-C-T

Variant names:

• chr22-21694573-C-T
• rs5999098
• NM_014337.4:c.1197-20C>T

Variant summary

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

The ENST00000398831.8(PPIL2):​c.1197-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,613,288 control chromosomes in the GnomAD database, including 96,778 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 0.37 (10506 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86272 hom.)
• Consequence: PPIL2 ENST00000398831.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 19 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398831.8. 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.1197-20C>T		intron	N/A	NP_055152.1
	PPIL2	NM_148176.3		c.1197-20C>T		intron	N/A	NP_680481.1
	PPIL2	NM_001317996.2		c.1197-20C>T		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.1197-20C>T		intron	N/A	ENSP00000381812.3
	PPIL2	ENST00000626352.2	TSL:1	c.1197-20C>T		intron	N/A	ENSP00000486725.1
	PPIL2	ENST00000335025.12	TSL:1	c.1197-20C>T		intron	N/A	ENSP00000334553.7

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56116 AN: 151856 Hom.: 10491 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.356

GnomAD2 exomes AF: 0.365 AC: 91589 AN: 250912 AF XY: 0.360

Gnomad AFR exome AF: 0.411

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.432

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.342 AC: 499075 AN: 1461314 Hom.: 86272 Cov.: 38 AF XY: 0.341 AC XY: 248018 AN XY: 726996

African (AFR) AF: 0.418 AC: 13975 AN: 33468

American (AMR) AF: 0.372 AC: 16623 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 10501 AN: 26120

East Asian (EAS) AF: 0.418 AC: 16603 AN: 39690

South Asian (SAS) AF: 0.328 AC: 28258 AN: 86222

European-Finnish (FIN) AF: 0.408 AC: 21699 AN: 53238

Middle Eastern (MID) AF: 0.320 AC: 1829 AN: 5718

European-Non Finnish (NFE) AF: 0.332 AC: 368695 AN: 1111788

Other (OTH) AF: 0.346 AC: 20892 AN: 60364

GnomAD4 genome AF: 0.370 AC: 56164 AN: 151974 Hom.: 10506 Cov.: 32 AF XY: 0.372 AC XY: 27651 AN XY: 74276

African (AFR) AF: 0.410 AC: 16981 AN: 41448

American (AMR) AF: 0.338 AC: 5163 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1459 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2209 AN: 5130

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4818

European-Finnish (FIN) AF: 0.433 AC: 4580 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23176 AN: 67954

Other (OTH) AF: 0.355 AC: 749 AN: 2112

Alfa AF: 0.350 Hom.: 26148

Bravo AF: 0.368

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.73
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5999098; hg19: chr22-22048862; COSMIC: COSV58608912; COSMIC: COSV58608912;