Genetic Variant PIN1:c.271+78C>T (chr19-9838726-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006221.4(PIN1):c.271+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,209,468 control chromosomes in the GnomAD database, including 36 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 0.0058 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 33 hom. )

Consequence

PIN1
NM_006221.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BS2

High AC in GnomAd4 at 884 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIN1	NM_006221.4	MANE Select	c.271+78C>T	intron	N/A	NP_006212.1	Q13526
PIN1	NR_038422.3		n.351+78C>T	intron	N/A
PIN1	NR_038830.2		n.351+78C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIN1	ENST00000247970.9	TSL:1 MANE Select	c.271+78C>T	intron	N/A	ENSP00000247970.5	Q13526
PIN1	ENST00000380889.6	TSL:1	n.1304+78C>T	intron	N/A
PIN1	ENST00000929406.1		c.316+33C>T	intron	N/A	ENSP00000599465.1

Frequencies

GnomAD3 genomes

AF:

0.00580

AC:

883

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00877

Gnomad OTH

AF:

0.00430

GnomAD4 exome

AF:

0.00668

AC:

7057

AN:

1057130

Hom.:

AF XY:

0.00672

AC XY:

3543

AN XY:

527258

show subpopulations

African (AFR)

AF:

0.000755

AC:

AN:

25154

American (AMR)

AF:

0.00243

AC:

AN:

32510

Ashkenazi Jewish (ASJ)

AF:

0.00694

AC:

143

AN:

20614

East Asian (EAS)

AF:

0.00

AC:

AN:

33820

South Asian (SAS)

AF:

0.00375

AC:

255

AN:

68042

European-Finnish (FIN)

AF:

0.00950

AC:

308

AN:

32424

Middle Eastern (MID)

AF:

0.00868

AC:

AN:

3686

European-Non Finnish (NFE)

AF:

0.00746

AC:

5925

AN:

794436

Other (OTH)

AF:

0.00637

AC:

296

AN:

46444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

370

740

1110

1480

1850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.00580

AC:

884

AN:

152338

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

448

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

41586

American (AMR)

AF:

0.00248

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00455

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0123

AC:

131

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00878

AC:

597

AN:

68030

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00682

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.7

(source)

DANN

Benign

0.61

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over