12-14567623-A-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024829.6(PLBD1):​c.74T>C​(p.Leu25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PLBD1
NM_024829.6 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.017659664).
BP6
Variant 12-14567623-A-G is Benign according to our data. Variant chr12-14567623-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3214347.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLBD1NM_024829.6 linkc.74T>C p.Leu25Pro missense_variant Exon 1 of 11 ENST00000240617.10 NP_079105.4 Q6P4A8
PLBD1-AS1NR_120465.1 linkn.-109A>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLBD1ENST00000240617.10 linkc.74T>C p.Leu25Pro missense_variant Exon 1 of 11 1 NM_024829.6 ENSP00000240617.5 Q6P4A8

Frequencies

GnomAD3 genomes
AF:
0.00161
AC:
30
AN:
18640
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00403
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000460
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:
0.00
Gnomad OTH
AF:
0.00481
GnomAD2 exomes
AF:
0.0000353
AC:
2
AN:
56624
AF XY:
0.0000605
show subpopulations
Gnomad AFR exome
AF:
0.000943
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000128
AC:
21
AN:
163834
Hom.:
0
Cov.:
0
AF XY:
0.000142
AC XY:
11
AN XY:
77628
show subpopulations
African (AFR)
AF:
0.00414
AC:
17
AN:
4106
American (AMR)
AF:
0.00
AC:
0
AN:
3328
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1798
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2020
South Asian (SAS)
AF:
0.00187
AC:
4
AN:
2138
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
3652
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
352
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
140304
Other (OTH)
AF:
0.00
AC:
0
AN:
6136
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00160
AC:
30
AN:
18692
Hom.:
0
Cov.:
0
AF XY:
0.00142
AC XY:
13
AN XY:
9156
show subpopulations
African (AFR)
AF:
0.00400
AC:
28
AN:
6996
American (AMR)
AF:
0.000459
AC:
1
AN:
2180
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
234
East Asian (EAS)
AF:
0.00
AC:
0
AN:
274
South Asian (SAS)
AF:
0.00
AC:
0
AN:
92
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
1448
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
22
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
7140
Other (OTH)
AF:
0.00481
AC:
1
AN:
208
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 09, 2024
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
9.1
DANN
Benign
0.51
DEOGEN2
Benign
0.0048
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.14
T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
PhyloP100
-0.58
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.54
N
REVEL
Benign
0.059
Sift
Benign
0.049
D
Sift4G
Benign
0.075
T
Polyphen
0.0
B
Vest4
0.21
MVP
0.067
MPC
0.32
ClinPred
0.013
T
GERP RS
-2.5
PromoterAI
-0.011
Neutral
Varity_R
0.084
gMVP
0.65
Mutation Taster
=93/7
polymorphism

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

Other links and lift over

dbSNP: rs773839439; hg19: chr12-14720557; COSMIC: COSV53692094; COSMIC: COSV53692094; API