dbSNP rs140494564: PIN4:c.-16A>G (chrX-72181770-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_006223.4(PIN4):c.-16A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,199,545 control chromosomes in the GnomAD database, including 2 homozygotes. There are 460 hemizygotes in GnomAD. 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 0.00081 ( 0 hom., 24 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 2 hom. 436 hem. )

Consequence

PIN4
NM_006223.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.710

Publications

0 publications found

Variant links:

Genes affected

PIN4 (HGNC:8992): (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria. [provided by RefSeq, Dec 2009]

PIN4 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=-0.81).

BS2

High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIN4	NM_006223.4 link	c.-16A>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000373669.8	NP_006214.3	Q9Y237-1
PIN4	NM_001170747.1 link	c.60A>G	p.Gln20Gln	synonymous_variant	Exon 1 of 4		NP_001164218.1	Q9Y237-3
PIN4	NR_033187.2 link	n.14A>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIN4	ENST00000373669.8 link	c.-16A>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_006223.4	ENSP00000362773.3		Q9Y237-1

Frequencies

GnomAD3 genomes

AF:

0.000811

AC:

AN:

112143

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000756

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000681

AC:

124

AN:

182203

AF XY:

0.000645

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.00139

AC:

1511

AN:

1087349

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

436

AN XY:

354215

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26242

American (AMR)

AF:

0.000199

AC:

AN:

35171

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19322

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.0000557

AC:

AN:

53828

European-Finnish (FIN)

AF:

0.0000987

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.000586

AC:

AN:

3415

European-Non Finnish (NFE)

AF:

0.00173

AC:

1439

AN:

832956

Other (OTH)

AF:

0.00116

AC:

AN:

45718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000811

AC:

AN:

112196

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

34360

show subpopulations

African (AFR)

AF:

0.000291

AC:

AN:

30882

American (AMR)

AF:

0.000755

AC:

AN:

10599

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

2738

European-Finnish (FIN)

AF:

0.000163

AC:

AN:

6117

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

53218

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000565

Hom.:

Bravo

AF:

0.000782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.8

(source)

DANN

Benign

0.62

PhyloP100

-0.71

PromoterAI

0.024

Neutral

(source)

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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rs140494564

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