19-9848202-A-G

Variant summary

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

The NM_006221.4(PIN1):c.382+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,001,368 control chromosomes in the GnomAD database, including 53,890 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 0.33 (8492 hom., cov: 32)
  • Exomes 𝑓: 0.32 (45398 hom.)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

PIN1 (HGNC:8988): (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) Peptidyl-prolyl cis/trans isomerases (PPIases) catalyze the cis/trans isomerization of peptidyl-prolyl peptide bonds. This gene encodes one of the PPIases, which specifically binds to phosphorylated ser/thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. The conformational regulation catalyzed by this PPIase has a profound impact on key proteins involved in the regulation of cell growth, genotoxic and other stress responses, the immune response, induction and maintenance of pluripotency, germ cell development, neuronal differentiation, and survival. This enzyme also plays a key role in the pathogenesis of Alzheimer's disease and many cancers. Multiple alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIN1	NM_006221.4	c.382+62A>G		intron_variant		ENST00000247970.9
PIN1	XM_011528068.3	c.397+62A>G		intron_variant
PIN1	NR_038422.3	n.462+62A>G		intron_variant, non_coding_transcript_variant
PIN1	NR_038830.2	n.462+62A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN1	ENST00000247970.9	c.382+62A>G		intron_variant		1	NM_006221.4	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50314 AN: 151936 Hom.: 8487 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.318 AC: 65672 AN: 206720 Hom.: 10584 AF XY: 0.327 AC XY: 36622 AN XY: 112070

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.271

Gnomad SAS exome AF: 0.397

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.320 AC: 271392 AN: 849314 Hom.: 45398 Cov.: 11 AF XY: 0.324 AC XY: 144169 AN XY: 444340

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.331 AC: 50337 AN: 152054 Hom.: 8492 Cov.: 32 AF XY: 0.331 AC XY: 24622 AN XY: 74318

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.312

Alfa AF: 0.265 Hom.: 1634

Bravo AF: 0.322

Asia WGS AF: 0.325 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.99
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2010457; hg19: chr19-9958878; COSMIC: COSV56112804;