rs79384503

Positions:

• chr22-21693680-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014337.4(PPIL2):​c.1140-136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 895,214 control chromosomes in the GnomAD database, including 18 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 0.0075 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (3 hom.)
• Consequence: PPIL2 NM_014337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00748 (1140/152314) while in subpopulation AFR AF= 0.0259 (1076/41566). AF 95% confidence interval is 0.0246. There are 15 homozygotes in gnomad4. There are 554 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL2	NM_014337.4	c.1140-136C>T		intron_variant		ENST00000398831.8	NP_055152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIL2	ENST00000398831.8	c.1140-136C>T		intron_variant		1	NM_014337.4	ENSP00000381812	P1

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1136 AN: 152196 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000937 AC: 696 AN: 742900 Hom.: 3 AF XY: 0.000761 AC XY: 296 AN XY: 388962

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000624

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000291

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00748 AC: 1140 AN: 152314 Hom.: 15 Cov.: 32 AF XY: 0.00744 AC XY: 554 AN XY: 74468

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00959 Hom.: 1

Bravo AF: 0.00873

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.72
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: rs79384503; hg19: chr22-22047969;