chr7-44800017-C-T

Variant names:

• chr7-44800017-C-T
• rs6463247
• NM_021130.5:c.362+143C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021130.5(PPIA):​c.362+143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 851,794 control chromosomes in the GnomAD database, including 247,805 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 0.64 (35534 hom., cov: 33)
  • Exomes 𝑓: 0.76 (212271 hom.)
• Consequence: PPIA NM_021130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIA	NM_021130.5	MANE Select	c.362+143C>T		intron	N/A	NP_066953.1
	PPIA	NM_001300981.2		c.182+143C>T		intron	N/A	NP_001287910.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIA	ENST00000468812.6	TSL:1 MANE Select	c.362+143C>T		intron	N/A	ENSP00000419425.1
	PPIA	ENST00000355968.10	TSL:1	c.182+143C>T		intron	N/A	ENSP00000430817.1
	PPIA	ENST00000678643.1		n.864C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97414 AN: 152048 Hom.: 35534 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.678

GnomAD4 exome AF: 0.761 AC: 532626 AN: 699628 Hom.: 212271 Cov.: 9 AF XY: 0.759 AC XY: 272461 AN XY: 358966

African (AFR) AF: 0.313 AC: 5424 AN: 17324

American (AMR) AF: 0.563 AC: 11938 AN: 21190

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 13538 AN: 15786

East Asian (EAS) AF: 0.201 AC: 6771 AN: 33622

South Asian (SAS) AF: 0.643 AC: 33989 AN: 52848

European-Finnish (FIN) AF: 0.867 AC: 27033 AN: 31194

Middle Eastern (MID) AF: 0.736 AC: 2167 AN: 2946

European-Non Finnish (NFE) AF: 0.829 AC: 406433 AN: 490298

Other (OTH) AF: 0.736 AC: 25333 AN: 34420

GnomAD4 genome AF: 0.640 AC: 97436 AN: 152166 Hom.: 35534 Cov.: 33 AF XY: 0.637 AC XY: 47392 AN XY: 74384

African (AFR) AF: 0.320 AC: 13294 AN: 41520

American (AMR) AF: 0.599 AC: 9147 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2933 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1209 AN: 5178

South Asian (SAS) AF: 0.628 AC: 3032 AN: 4828

European-Finnish (FIN) AF: 0.867 AC: 9173 AN: 10582

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56339 AN: 68002

Other (OTH) AF: 0.677 AC: 1430 AN: 2112

Alfa AF: 0.754 Hom.: 57474

Bravo AF: 0.604

Asia WGS AF: 0.454 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		-0.075
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs6463247; hg19: chr7-44839616; COSMIC: COSV63533969; COSMIC: COSV63533969;