rs889162

Variant names:

• chr19-9841240-C-T
• rs889162
• NM_006221.4:c.271+2592C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006221.4(PIN1):​c.271+2592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,142 control chromosomes in the GnomAD database, including 2,958 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 0.19 (2958 hom., cov: 32)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006221.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	NM_006221.4	MANE Select	c.271+2592C>T		intron	N/A	NP_006212.1	Q13526
	PIN1	NR_038422.3		n.351+2592C>T		intron	N/A
	PIN1	NR_038830.2		n.351+2592C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1	ENST00000247970.9	TSL:1 MANE Select	c.271+2592C>T		intron	N/A	ENSP00000247970.5	Q13526
	PIN1	ENST00000380889.6	TSL:1	n.1304+2592C>T		intron	N/A
	PIN1	ENST00000929406.1		c.316+2547C>T		intron	N/A	ENSP00000599465.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28251 AN: 152024 Hom.: 2958 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28255 AN: 152142 Hom.: 2958 Cov.: 32 AF XY: 0.187 AC XY: 13915 AN XY: 74350

African (AFR) AF: 0.102 AC: 4228 AN: 41520

American (AMR) AF: 0.151 AC: 2300 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5178

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4826

European-Finnish (FIN) AF: 0.285 AC: 3012 AN: 10578

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15060 AN: 67976

Other (OTH) AF: 0.165 AC: 348 AN: 2114

Alfa AF: 0.208 Hom.: 14518

Bravo AF: 0.173

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs889162; hg19: chr19-9951916;