22-21693680-C-T

Variant names:

• chr22-21693680-C-T
• rs79384503
• NM_014337.4:c.1140-136C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.84).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	NM_014337.4	MANE Select	c.1140-136C>T		intron	N/A	NP_055152.1	Q13356-1
	PPIL2	NM_148176.3		c.1140-136C>T		intron	N/A	NP_680481.1	Q13356-2
	PPIL2	NM_001317996.2		c.1140-136C>T		intron	N/A	NP_001304925.1	Q13356-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.1140-136C>T		intron	N/A	ENSP00000381812.3	Q13356-1
	PPIL2	ENST00000626352.2	TSL:1	c.1140-136C>T		intron	N/A	ENSP00000486725.1	Q13356-2
	PPIL2	ENST00000335025.12	TSL:1	c.1140-136C>T		intron	N/A	ENSP00000334553.7	Q13356-1

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

African (AFR) AF: 0.0283 AC: 549 AN: 19406

American (AMR) AF: 0.00154 AC: 60 AN: 39046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17958

East Asian (EAS) AF: 0.00 AC: 0 AN: 35258

South Asian (SAS) AF: 0.0000624 AC: 4 AN: 64054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46374

Middle Eastern (MID) AF: 0.00321 AC: 11 AN: 3432

European-Non Finnish (NFE) AF: 0.0000291 AC: 14 AN: 481764

Other (OTH) AF: 0.00163 AC: 58 AN: 35608

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

African (AFR) AF: 0.0259 AC: 1076 AN: 41566

American (AMR) AF: 0.00301 AC: 46 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00607 Hom.: 1

Bravo AF: 0.00873

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.72
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs79384503; hg19: chr22-22047969;