Genetic Variant PIP:p.Ile142Ile (chr7-143139627-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002652.3(PIP):c.426C>A(p.Ile142Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,611,050 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 17 hom. )

Consequence

PIP
NM_002652.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.891

Variant links:

Genes affected

PIP (HGNC:8993): (prolactin induced protein) Enables IgG binding activity; aspartic-type endopeptidase activity; and identical protein binding activity. Involved in several processes, including detection of chemical stimulus involved in sensory perception of bitter taste; negative regulation of T cell apoptotic process; and proteolysis. Located in extracellular space and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PIP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-143139627-C-A is Benign according to our data. Variant chr7-143139627-C-A is described in ClinVar as [Benign]. Clinvar id is 712563.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.891 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP	NM_002652.3 link	c.426C>A	p.Ile142Ile	synonymous_variant	Exon 4 of 4	ENST00000291009.4	NP_002643.1	P12273

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP	ENST00000291009.4 link	c.426C>A	p.Ile142Ile	synonymous_variant	Exon 4 of 4	1	NM_002652.3	ENSP00000291009.3		P12273

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000765

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00298

AC:

750

AN:

251296

Hom.:

AF XY:

0.00266

AC XY:

361

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.000889

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00114

AC:

1662

AN:

1458952

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

824

AN XY:

725554

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.0000768

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00246

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.000594

Gnomad4 OTH exome

AF:

0.000913

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152098

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000723

Gnomad4 AMR

AF:

0.00439

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00255

Gnomad4 NFE

AF:

0.000765

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000945

Hom.:

Bravo

AF:

0.00151

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000766

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.10

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over