rs8207

Positions:

• chr2-169637353-A-G

Variant summary

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

The NM_004792.3(PPIG):​c.2095A>G​(p.Asn699Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,609,656 control chromosomes in the GnomAD database, including 53,281 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4753 hom., cov: 31)
  • Exomes 𝑓: 0.25 (48528 hom.)
• Consequence: PPIG NM_004792.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

Genes affected

PPIG (HGNC:14650): (peptidylprolyl isomerase G) Enables cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Involved in protein peptidyl-prolyl isomerization. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027493238).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIG	NM_004792.3	c.2095A>G	p.Asn699Asp	missense_variant	14/14	ENST00000260970.8
PPIG	XM_005246966.3	c.2095A>G	p.Asn699Asp	missense_variant	14/14
PPIG	XM_005246967.2	c.2095A>G	p.Asn699Asp	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIG	ENST00000260970.8	c.2095A>G	p.Asn699Asp	missense_variant	14/14	1	NM_004792.3	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37162 AN: 151944 Hom.: 4754 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0479

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.222 AC: 54992 AN: 247314 Hom.: 6859 AF XY: 0.228 AC XY: 30480 AN XY: 133738

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.0506

Gnomad SAS exome AF: 0.235

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.252 AC: 367596 AN: 1457594 Hom.: 48528 Cov.: 36 AF XY: 0.252 AC XY: 182576 AN XY: 724944

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.0355

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.244 AC: 37176 AN: 152062 Hom.: 4753 Cov.: 31 AF XY: 0.239 AC XY: 17740 AN XY: 74362

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0480

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.243

Alfa AF: 0.259 Hom.: 12870

Bravo AF: 0.238

TwinsUK AF: 0.276 AC: 1022

ALSPAC AF: 0.263 AC: 1015

ESP6500AA AF: 0.269 AC: 1184

ESP6500EA AF: 0.271 AC: 2331

ExAC AF: 0.231 AC: 28002

Asia WGS AF: 0.161 AC: 563 AN: 3478

EpiCase AF: 0.273

EpiControl AF: 0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	0.91	P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.010	N;N;N
REVEL	Benign	0.098
Sift	Uncertain	0.022	D;D;D
Sift4G	Benign	0.35	T;T;T
Polyphen		0.016	B;B;B
Vest4		0.098
MPC		0.040
ClinPred		0.0058	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.017

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: rs8207; hg19: chr2-170493863; COSMIC: COSV53645229; COSMIC: COSV53645229;