dbSNP rs75778757: PLBD1:p.Arg438Gln (chr12-14506992-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024829.6(PLBD1):c.1313G>A(p.Arg438Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,944 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 60 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.38

Publications

10 publications found

Variant links:

Genes affected

PLBD1 (HGNC:26215): (phospholipase B domain containing 1) Predicted to enable phospholipase activity. Predicted to be involved in phospholipid catabolic process. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PLBD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01349023).

BP6

Variant 12-14506992-C-T is Benign according to our data. Variant chr12-14506992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642755.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLBD1	NM_024829.6 link	c.1313G>A	p.Arg438Gln	missense_variant	Exon 9 of 11	ENST00000240617.10	NP_079105.4	Q6P4A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLBD1	ENST00000240617.10 link	c.1313G>A	p.Arg438Gln	missense_variant	Exon 9 of 11	1	NM_024829.6	ENSP00000240617.5		Q6P4A8

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00737

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00809

Gnomad OTH

AF:

0.00528

GnomAD2 exomes

AF:

0.00612

AC:

1539

AN:

251348

AF XY:

0.00593

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0428

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00674

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00489

AC:

7152

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

3567

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.00248

AC:

111

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

1064

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00640

AC:

342

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00471

AC:

5236

AN:

1111962

Other (OTH)

AF:

0.00604

AC:

365

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

353

706

1059

1412

1765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00588

AC:

894

AN:

152118

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

426

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000939

AC:

AN:

41514

American (AMR)

AF:

0.00458

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3468

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00737

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00809

AC:

550

AN:

67998

Other (OTH)

AF:

0.00523

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

140

186

233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00785

Hom.:

Bravo

AF:

0.00502

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00590

AC:

716

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00587

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PLBD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.8

PhyloP100

7.4

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.53

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MVP

0.55

MPC

0.84

ClinPred

0.040

GERP RS

5.4

Varity_R

0.63

gMVP

0.74

Mutation Taster

=82/18

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

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rs75778757

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over