rs1077220

Positions:

• chr19-9836241-A-G
• chr19-9836241-A-T

Variant summary

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

The ENST00000247970.9(PIN1):​c.58+839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,548 control chromosomes in the GnomAD database, including 42,398 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 0.74 (42262 hom., cov: 32)
  • Exomes 𝑓: 0.76 (136 hom.)
• Consequence: PIN1 ENST00000247970.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIN1	NM_006221.4	c.58+839A>G		intron_variant		ENST00000247970.9	NP_006212.1
PIN1	XM_011528068.3	c.-44-582A>G		intron_variant			XP_011526370.1
PIN1	NR_038422.3	n.86-582A>G		intron_variant, non_coding_transcript_variant
PIN1	NR_038830.2	n.86-582A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9	c.58+839A>G		intron_variant		1	NM_006221.4	ENSP00000247970	P1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112745 AN: 151982 Hom.: 42250 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.757 AC: 339 AN: 448 Hom.: 136 Cov.: 0 AF XY: 0.763 AC XY: 206 AN XY: 270

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.676

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.722

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.804

Gnomad4 OTH exome AF: 0.636

GnomAD4 genome AF: 0.742 AC: 112809 AN: 152100 Hom.: 42262 Cov.: 32 AF XY: 0.737 AC XY: 54793 AN XY: 74344

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.749

Alfa AF: 0.772 Hom.: 44891

Bravo AF: 0.745

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.81

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: rs1077220; hg19: chr19-9946917;