chr7-44796715-A-G

Variant names:

• chr7-44796715-A-G
• rs6850
• NM_021130.5:c.-10A>G

Variant summary

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

The NM_021130.5(PPIA):​c.-10A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,608,180 control chromosomes in the GnomAD database, including 40,964 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 0.26 (7445 hom., cov: 34)
  • Exomes 𝑓: 0.17 (33519 hom.)
• Consequence: PPIA NM_021130.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 25 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]

ENSG00000297670 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIA	NM_021130.5	c.-10A>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000468812.6	NP_066953.1
PPIA	NM_001300981.2	c.-347A>G		5_prime_UTR_variant	Exon 1 of 6		NP_001287910.1
LOC105375259	XR_007060300.1	n.-185T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIA	ENST00000468812.6	c.-10A>G		5_prime_UTR_variant	Exon 1 of 5	1	NM_021130.5	ENSP00000419425.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39629 AN: 152084 Hom.: 7436 Cov.: 34

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.256 AC: 63537 AN: 247874 AF XY: 0.246

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.738

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.170 AC: 247878 AN: 1455982 Hom.: 33519 Cov.: 33 AF XY: 0.173 AC XY: 125074 AN XY: 724564

African (AFR) AF: 0.459 AC: 15054 AN: 32810

American (AMR) AF: 0.387 AC: 17257 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3831 AN: 26042

East Asian (EAS) AF: 0.773 AC: 30371 AN: 39280

South Asian (SAS) AF: 0.326 AC: 28021 AN: 86070

European-Finnish (FIN) AF: 0.123 AC: 6508 AN: 53068

Middle Eastern (MID) AF: 0.204 AC: 984 AN: 4818

European-Non Finnish (NFE) AF: 0.121 AC: 133858 AN: 1109194

Other (OTH) AF: 0.200 AC: 11994 AN: 60076

GnomAD4 genome AF: 0.261 AC: 39677 AN: 152198 Hom.: 7445 Cov.: 34 AF XY: 0.266 AC XY: 19826 AN XY: 74414

African (AFR) AF: 0.444 AC: 18446 AN: 41514

American (AMR) AF: 0.319 AC: 4875 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3798 AN: 5154

South Asian (SAS) AF: 0.348 AC: 1680 AN: 4834

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10606

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8247 AN: 68006

Other (OTH) AF: 0.248 AC: 525 AN: 2116

Alfa AF: 0.196 Hom.: 1216

Bravo AF: 0.285

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.37
DANN	Benign	0.39
PhyloP100		-1.7
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=300/0	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: rs6850; hg19: chr7-44836314;