rs6970925

Positions:

• chr7-44797699-G-A
• chr7-44797699-G-C
• chr7-44797699-G-T

Variant summary

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

The NM_021130.5(PPIA):​c.69+906G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,186 control chromosomes in the GnomAD database, including 36,697 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 0.69 (36697 hom., cov: 34)
• Consequence: PPIA NM_021130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

Genes affected

PPIA (HGNC:9253): (peptidylprolyl isomerase A) This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIA	NM_021130.5	c.69+906G>A		intron_variant		ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2	c.-269+906G>A		intron_variant			NP_001287910.1
PPIA	XM_047420536.1	c.-269+78G>A		intron_variant			XP_047276492.1
PPIA	XM_047420537.1	c.-179+78G>A		intron_variant			XP_047276493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812.6	c.69+906G>A		intron_variant		1	NM_021130.5	ENSP00000419425	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104167 AN: 152068 Hom.: 36652 Cov.: 34

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.686

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.685 AC: 104270 AN: 152186 Hom.: 36697 Cov.: 34 AF XY: 0.688 AC XY: 51160 AN XY: 74404

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.691

Alfa AF: 0.624 Hom.: 27209

Bravo AF: 0.705

Asia WGS AF: 0.808 AC: 2809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.73
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: rs6970925; hg19: chr7-44837298;