Genetic Variant NM_004792.3:c.1485A>G (chr2-169636743-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004792.3(PPIG):c.1485A>G(p.Glu495Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,612,472 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 78 hom. )

Consequence

PPIG
NM_004792.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0870

Variant links:

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]

PPIG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 2-169636743-A-G is Benign according to our data. Variant chr2-169636743-A-G is described in ClinVar as [Benign]. Clinvar id is 785854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00383 (583/152242) while in subpopulation AMR AF= 0.0254 (387/15266). AF 95% confidence interval is 0.0233. There are 10 homozygotes in gnomad4. There are 308 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 583 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3 link	c.1485A>G	p.Glu495Glu	synonymous_variant	Exon 14 of 14	ENST00000260970.8	NP_004783.2	Q13427-1
PPIG	XM_005246966.3 link	c.1485A>G	p.Glu495Glu	synonymous_variant	Exon 14 of 14		XP_005247023.1	Q13427-1
PPIG	XM_005246967.2 link	c.1485A>G	p.Glu495Glu	synonymous_variant	Exon 14 of 14		XP_005247024.1	Q13427-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8 link	c.1485A>G	p.Glu495Glu	synonymous_variant	Exon 14 of 14	1	NM_004792.3	ENSP00000260970.3		Q13427-1

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

581

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00782

AC:

1920

AN:

245368

Hom.:

AF XY:

0.00644

AC XY:

861

AN XY:

133614

show subpopulations

Gnomad AFR exome

AF:

0.000459

Gnomad AMR exome

AF:

0.0405

Gnomad ASJ exome

AF:

0.00304

Gnomad EAS exome

AF:

0.0235

Gnomad SAS exome

AF:

0.000364

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000236

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00236

AC:

3448

AN:

1460230

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1601

AN XY:

726376

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.0393

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.0333

Gnomad4 SAS exome

AF:

0.000396

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00383

AC:

583

AN:

152242

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0231

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00544

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.3

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over