20-8132669-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_015192.4(PLCB1):​c.18C>T​(p.Pro6Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,611,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PLCB1
NM_015192.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.926

Publications

0 publications found
Variant links:
Genes affected
PLCB1 (HGNC:15917): (phospholipase C beta 1) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PLCB1 Gene-Disease associations (from GenCC):
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 12
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • infantile spasms
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • malignant migrating partial seizures of infancy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 20-8132669-C-T is Benign according to our data. Variant chr20-8132669-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1012476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.926 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCB1NM_015192.4 linkc.18C>T p.Pro6Pro synonymous_variant Exon 1 of 32 ENST00000338037.11 NP_056007.1 Q9NQ66-1
PLCB1NM_182734.3 linkc.18C>T p.Pro6Pro synonymous_variant Exon 1 of 33 NP_877398.1 Q9NQ66-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCB1ENST00000338037.11 linkc.18C>T p.Pro6Pro synonymous_variant Exon 1 of 32 1 NM_015192.4 ENSP00000338185.6 Q9NQ66-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000811
AC:
2
AN:
246516
AF XY:
0.0000149
show subpopulations
Gnomad AFR exome
AF:
0.0000635
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:
0.00000904
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1459678
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726186
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33334
American (AMR)
AF:
0.00
AC:
0
AN:
44584
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26056
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39616
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86064
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53118
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.0000117
AC:
13
AN:
1110918
Other (OTH)
AF:
0.00
AC:
0
AN:
60244
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
1
2
3
4
5
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:
0.0000197
AC:
3
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41448
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
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:
0.0000580
Hom.:
0
Bravo
AF:
0.0000227
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

PLCB1: BP4, BP7 -

Developmental and epileptic encephalopathy, 12 Benign:1
Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
CADD
Benign
12
DANN
Benign
0.97
PhyloP100
-0.93
PromoterAI
-0.056
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs745497485; hg19: chr20-8113316; API