dbSNP rs1077220: PIN1:c.58+839A>G (chr19-9836241-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006221.4(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
NM_006221.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0520

Publications

7 publications found

Variant links:

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]

PIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
PIN1	NM_006221.4 link	c.58+839A>G	intron_variant	Intron 1 of 3	ENST00000247970.9	NP_006212.1	Q13526
PIN1	NR_038422.3 link	n.86-582A>G	intron_variant	Intron 1 of 4
PIN1	NR_038830.2 link	n.86-582A>G	intron_variant	Intron 1 of 5
PIN1	XM_011528068.3 link	c.-44-582A>G	intron_variant	Intron 1 of 5		XP_011526370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN1	ENST00000247970.9 link	c.58+839A>G		intron_variant	Intron 1 of 3	1	NM_006221.4	ENSP00000247970.5		Q13526

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112745

AN:

151982

Hom.:

42250

Cov.:

show subpopulations

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.:

AF XY:

0.763

AC XY:

206

AN XY:

270

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.676

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.722

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.804

AC:

238

AN:

296

Other (OTH)

AF:

0.636

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.742

AC:

112809

AN:

152100

Hom.:

42262

Cov.:

AF XY:

0.737

AC XY:

54793

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.748

AC:

31014

AN:

41484

American (AMR)

AF:

0.763

AC:

11661

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

2793

AN:

3472

East Asian (EAS)

AF:

0.427

AC:

2204

AN:

5164

South Asian (SAS)

AF:

0.603

AC:

2911

AN:

4824

European-Finnish (FIN)

AF:

0.702

AC:

7418

AN:

10568

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.771

AC:

52420

AN:

67984

Other (OTH)

AF:

0.749

AC:

1581

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1478

2956

4435

5913

7391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.769

Hom.:

58192

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

(source)

DANN

Benign

0.81

PhyloP100

0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over