19-9841240-C-T

Position:

• chr19-9841240-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIN1	NM_006221.4	c.271+2592C>T		intron_variant		ENST00000247970.9	NP_006212.1
PIN1	XM_011528068.3	c.286+2592C>T		intron_variant			XP_011526370.1
PIN1	NR_038422.3	n.351+2592C>T		intron_variant, non_coding_transcript_variant
PIN1	NR_038830.2	n.351+2592C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9	c.271+2592C>T		intron_variant		1	NM_006221.4	ENSP00000247970	P1

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.165

Alfa AF: 0.208 Hom.: 7185

Bravo AF: 0.173

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.78

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: rs889162; hg19: chr19-9951916;