Variant 19-17360554-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031310.3(PLVAP):c.1296T>C(p.Pro432=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,614,030 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 9 hom., cov: 31)

Exomes 𝑓: 0.013 ( 176 hom. )

Consequence

PLVAP
NM_031310.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

PLVAP (HGNC:13635): (plasmalemma vesicle associated protein) Predicted to enable identical protein binding activity. Involved in MAPK cascade; positive regulation of cellular extravasation; and tumor necrosis factor-mediated signaling pathway. Located in cell surface. Colocalizes with caveola. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Apr 2022]

PLVAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-17360554-A-G is Benign according to our data. Variant chr19-17360554-A-G is described in ClinVar as [Benign]. Clinvar id is 1694906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLVAP	NM_031310.3 linkuse as main transcript	c.1296T>C	p.Pro432=	synonymous_variant	5/6	ENST00000252590.9	NP_112600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLVAP	ENST00000252590.9 linkuse as main transcript	c.1296T>C	p.Pro432=	synonymous_variant	5/6	1	NM_031310.3	ENSP00000252590	P1
PLVAP	ENST00000595816.1 linkuse as main transcript	c.79+5419T>C		intron_variant		3		ENSP00000469369

Frequencies

GnomAD3 genomes

AF:

0.00926

AC:

1409

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00969

AC:

2433

AN:

251062

Hom.:

AF XY:

0.00974

AC XY:

1321

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.00696

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00718

GnomAD4 exome

AF:

0.0130

AC:

18931

AN:

1461716

Hom.:

176

Cov.:

AF XY:

0.0127

AC XY:

9207

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00230

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00624

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00381

Gnomad4 FIN exome

AF:

0.0184

Gnomad4 NFE exome

AF:

0.0147

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.00924

AC:

1408

AN:

152314

Hom.:

Cov.:

AF XY:

0.00984

AC XY:

733

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00781

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	PLVAP: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

PLVAP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

DANN

Benign

0.58

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