Genetic Variant PLBD1:p.Leu25Gln (chr12-14567623-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024829.6(PLBD1):c.74T>A(p.Leu25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L25P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.579

Publications

2 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:

PLBD1-AS1 (HGNC:51143): (PLBD1 antisense RNA 1)

PLBD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002184689).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024829.6. 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
	PLBD1	NM_024829.6	MANE Select	c.74T>A	p.Leu25Gln	missense	Exon 1 of 11	NP_079105.4
	PLBD1-AS1	NR_120465.1		n.-109A>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLBD1	ENST00000240617.10	TSL:1 MANE Select	c.74T>A	p.Leu25Gln	missense	Exon 1 of 11	ENSP00000240617.5	Q6P4A8
PLBD1	ENST00000918098.1		c.74T>A	p.Leu25Gln	missense	Exon 1 of 12	ENSP00000588157.1
PLBD1	ENST00000945093.1		c.74T>A	p.Leu25Gln	missense	Exon 1 of 11	ENSP00000615152.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

18628

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:

0.000280

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000777

AC:

AN:

56624

AF XY:

0.000786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000988

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.000645

AC:

101

AN:

156522

Hom.:

Cov.:

AF XY:

0.000770

AC XY:

AN XY:

74070

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

4096

American (AMR)

AF:

0.00906

AC:

AN:

3092

Ashkenazi Jewish (ASJ)

AF:

0.00117

AC:

AN:

1710

East Asian (EAS)

AF:

0.00209

AC:

AN:

1910

South Asian (SAS)

AF:

0.00349

AC:

AN:

2006

European-Finnish (FIN)

AF:

0.000593

AC:

AN:

3374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

342

European-Non Finnish (NFE)

AF:

0.000395

AC:

AN:

134154

Other (OTH)

AF:

0.000856

AC:

AN:

5838

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.281

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:

0.000107

AC:

AN:

18628

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

9106

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6950

American (AMR)

AF:

0.00

AC:

AN:

2174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

234

East Asian (EAS)

AF:

0.00

AC:

AN:

274

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000280

AC:

AN:

7138

Other (OTH)

AF:

0.00

AC:

AN:

208

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.141

AC:

727

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.9

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0035

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.41

PhyloP100

-0.58

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.49

REVEL

Benign

0.037

Sift

Benign

0.059

Sift4G

Benign

0.094

Polyphen

0.0030

Vest4

0.11

MutPred

0.51

Gain of sheet (P = 0.0344)

MPC

0.21

ClinPred

0.0099

GERP RS

-2.5

PromoterAI

-0.081

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.077

gMVP

0.61

Mutation Taster

=95/5

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