rs1985604

Positions:

• chr19-9842067-G-A
• chr19-9842067-G-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+3419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,224 control chromosomes in the GnomAD database, including 859 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 0.098 (859 hom., cov: 33)
• Consequence: PIN1 NM_006221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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 (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIN1	NM_006221.4	c.271+3419G>A		intron_variant		ENST00000247970.9
PIN1	XM_011528068.3	c.286+3419G>A		intron_variant
PIN1	NR_038422.3	n.351+3419G>A		intron_variant, non_coding_transcript_variant
PIN1	NR_038830.2	n.351+3419G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIN1	ENST00000247970.9	c.271+3419G>A		intron_variant		1	NM_006221.4	P1

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14867 AN: 152106 Hom.: 861 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.0976 AC: 14858 AN: 152224 Hom.: 859 Cov.: 33 AF XY: 0.0981 AC XY: 7302 AN XY: 74424

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0969

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0280 Hom.: 23

Bravo AF: 0.0936

Asia WGS AF: 0.0980 AC: 338 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	0.38
DANN	Benign	0.61

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: rs1985604; hg19: chr19-9952743;