rs8207

Variant names:

• chr2-169637353-A-G
• rs8207
• NM_004792.3:c.2095A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.2095A>G	p.Asn699Asp	missense_variant	Exon 14 of 14	ENST00000260970.8	NP_004783.2
PPIG	XM_005246966.3	c.2095A>G	p.Asn699Asp	missense_variant	Exon 14 of 14		XP_005247023.1
PPIG	XM_005246967.2	c.2095A>G	p.Asn699Asp	missense_variant	Exon 14 of 14		XP_005247024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.2095A>G	p.Asn699Asp	missense_variant	Exon 14 of 14	1	NM_004792.3	ENSP00000260970.3

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

GnomAD2 exomes AF: 0.222 AC: 54992 AN: 247314 AF XY: 0.228

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 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

African (AFR) AF: 0.260 AC: 8620 AN: 33120

American (AMR) AF: 0.117 AC: 5166 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6735 AN: 25988

East Asian (EAS) AF: 0.0355 AC: 1408 AN: 39666

South Asian (SAS) AF: 0.232 AC: 19720 AN: 85026

European-Finnish (FIN) AF: 0.219 AC: 11678 AN: 53338

Middle Eastern (MID) AF: 0.297 AC: 1530 AN: 5156

European-Non Finnish (NFE) AF: 0.268 AC: 297946 AN: 1111034

Other (OTH) AF: 0.246 AC: 14793 AN: 60196

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

African (AFR) AF: 0.260 AC: 10783 AN: 41486

American (AMR) AF: 0.165 AC: 2518 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 896 AN: 3466

East Asian (EAS) AF: 0.0480 AC: 249 AN: 5186

South Asian (SAS) AF: 0.233 AC: 1126 AN: 4830

European-Finnish (FIN) AF: 0.204 AC: 2164 AN: 10586

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18614 AN: 67916

Other (OTH) AF: 0.243 AC: 513 AN: 2114

Alfa AF: 0.258 Hom.: 23588

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
LIST_S2	Benign	0.69	.;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;N
PhyloP100		2.2
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
Mutation Taster		=99/1	polymorphism (auto)

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