rs2233683

Positions:

• chr19-9838726-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006221.4(PIN1):​c.271+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,209,468 control chromosomes in the GnomAD database, including 36 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 0.0058 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (33 hom.)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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]

PIN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High AC in GnomAd4 at 884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIN1	NM_006221.4	c.271+78C>T		intron_variant		ENST00000247970.9	NP_006212.1
PIN1	XM_011528068.3	c.286+78C>T		intron_variant			XP_011526370.1
PIN1	NR_038422.3	n.351+78C>T		intron_variant
PIN1	NR_038830.2	n.351+78C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9	c.271+78C>T		intron_variant		1	NM_006221.4	ENSP00000247970.5

Frequencies

GnomAD3 genomes AF: 0.00580 AC: 883 AN: 152220 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00877

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00668 AC: 7057 AN: 1057130 Hom.: 33 AF XY: 0.00672 AC XY: 3543 AN XY: 527258

Gnomad4 AFR exome AF: 0.000755

Gnomad4 AMR exome AF: 0.00243

Gnomad4 ASJ exome AF: 0.00694

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00375

Gnomad4 FIN exome AF: 0.00950

Gnomad4 NFE exome AF: 0.00746

Gnomad4 OTH exome AF: 0.00637

GnomAD4 genome AF: 0.00580 AC: 884 AN: 152338 Hom.: 3 Cov.: 32 AF XY: 0.00601 AC XY: 448 AN XY: 74486

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00878

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00682 Hom.: 1

Bravo AF: 0.00458

Asia WGS AF: 0.00115 AC: 4 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	2.7
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2233683; hg19: chr19-9949402;