rs2287838

chr19-9848338-G-Achr19-9848338-G-Cchr19-9848338-G-T

Variant summary

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

The NM_006221.4(PIN1):c.382+198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 592,752 control chromosomes in the GnomAD database, including 70,989 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 0.41 (15450 hom., cov: 33)
  • Exomes 𝑓: 0.49 (55539 hom.)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIN1	NM_006221.4	c.382+198G>A		intron_variant		ENST00000247970.9
PIN1	XM_011528068.3	c.397+198G>A		intron_variant
PIN1	NR_038422.3	n.462+198G>A		intron_variant, non_coding_transcript_variant
PIN1	NR_038830.2	n.462+198G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN1	ENST00000247970.9	c.382+198G>A		intron_variant		1	NM_006221.4	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61866 AN: 151942 Hom.: 15454 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.488 AC: 214873 AN: 440694 Hom.: 55539 Cov.: 2 AF XY: 0.478 AC XY: 111584 AN XY: 233478

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.407 AC: 61861 AN: 152058 Hom.: 15450 Cov.: 33 AF XY: 0.406 AC XY: 30179 AN XY: 74322

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.421

Alfa AF: 0.481 Hom.: 2463

Bravo AF: 0.397

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.32

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: rs2287838; hg19: chr19-9959014;