rs372802462

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_031310.3(PLVAP):c.1274T>C(p.Ile425Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

PLVAP
NM_031310.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.84

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

diarrhea 10, protein-losing enteropathy type
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
congenital diarrhea 7 with exudative enteropathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PLVAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39697927).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000591 (9/152172) while in subpopulation NFE AF = 0.000118 (8/68026). AF 95% confidence interval is 0.0000584. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031310.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLVAP	NM_031310.3	MANE Select	c.1274T>C	p.Ile425Thr	missense	Exon 5 of 6	NP_112600.1	Q9BX97

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLVAP	ENST00000252590.9	TSL:1 MANE Select	c.1274T>C	p.Ile425Thr	missense	Exon 5 of 6	ENSP00000252590.3	Q9BX97
PLVAP	ENST00000962152.1		c.1274T>C	p.Ile425Thr	missense	Exon 5 of 7	ENSP00000632211.1
PLVAP	ENST00000962153.1		c.1268T>C	p.Ile423Thr	missense	Exon 5 of 6	ENSP00000632212.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

250660

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1461530

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000899

AC:

100

AN:

1111846

Other (OTH)

AF:

0.0000166

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000591

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000889

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.75

M_CAP

Benign

0.018

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

3.8

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.8

REVEL

Benign

0.21

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.016

Polyphen

0.32

Vest4

0.64

MVP

0.22

MPC

0.88

ClinPred

0.21

GERP RS

3.5

Varity_R

0.17

gMVP

0.32

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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