rs2233681

chr19-9835259-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000592184.1(PIN1):n.3G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,255,880 control chromosomes in the GnomAD database, including 27 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 0.0025 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00067 (12 hom.)
• Consequence: PIN1 ENST00000592184.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.77).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0025 (381/152354) while in subpopulation AMR AF= 0.0235 (359/15304). AF 95% confidence interval is 0.0215. There are 15 homozygotes in gnomad4. There are 232 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 381 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN1	ENST00000592184.1	n.3G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 381 AN: 152240 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00389 AC: 413 AN: 106072 Hom.: 5 AF XY: 0.00266 AC XY: 157 AN XY: 59014

Gnomad AFR exome AF: 0.000435

Gnomad AMR exome AF: 0.0189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00337

GnomAD4 exome AF: 0.000667 AC: 736 AN: 1103526 Hom.: 12 Cov.: 15 AF XY: 0.000548 AC XY: 304 AN XY: 555048

Gnomad4 AFR exome AF: 0.000347

Gnomad4 AMR exome AF: 0.0210

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000597

Gnomad4 OTH exome AF: 0.000768

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152354 Hom.: 15 Cov.: 33 AF XY: 0.00311 AC XY: 232 AN XY: 74508

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00118 Hom.: 5

Bravo AF: 0.00306

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.062
Dann	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2233681; hg19: chr19-9945935;