rs2076413

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015192.4(PLCB1):c.2565G>A(p.Ala855Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,611,358 control chromosomes in the GnomAD database, including 71,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A855A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.25 ( 5232 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66464 hom. )

Consequence

PLCB1
NM_015192.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.138

Publications

21 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

PLCB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 20-8757087-G-A is Benign according to our data. Variant chr20-8757087-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.138 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.2565G>A	p.Ala855Ala	synonymous_variant	Exon 24 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3 link	c.2565G>A	p.Ala855Ala	synonymous_variant	Exon 24 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 link	c.2565G>A	p.Ala855Ala	synonymous_variant	Exon 24 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37699

AN:

151880

Hom.:

5232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.270

AC:

67806

AN:

250748

AF XY:

0.278

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.298

AC:

434946

AN:

1459360

Hom.:

66464

Cov.:

AF XY:

0.300

AC XY:

217684

AN XY:

726034

show subpopulations

African (AFR)

AF:

0.129

AC:

4325

AN:

33450

American (AMR)

AF:

0.199

AC:

8863

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

7920

AN:

26098

East Asian (EAS)

AF:

0.155

AC:

6165

AN:

39666

South Asian (SAS)

AF:

0.302

AC:

26000

AN:

85958

European-Finnish (FIN)

AF:

0.289

AC:

15425

AN:

53362

Middle Eastern (MID)

AF:

0.228

AC:

1313

AN:

5754

European-Non Finnish (NFE)

AF:

0.313

AC:

347751

AN:

1110134

Other (OTH)

AF:

0.285

AC:

17184

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

14264

28528

42793

57057

71321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11118

22236

33354

44472

55590

<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:

0.248

AC:

37707

AN:

151998

Hom.:

5232

Cov.:

AF XY:

0.247

AC XY:

18371

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.135

AC:

5592

AN:

41466

American (AMR)

AF:

0.217

AC:

3321

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

963

AN:

3468

East Asian (EAS)

AF:

0.154

AC:

796

AN:

5156

South Asian (SAS)

AF:

0.309

AC:

1489

AN:

4814

European-Finnish (FIN)

AF:

0.299

AC:

3156

AN:

10544

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21641

AN:

67960

Other (OTH)

AF:

0.231

AC:

488

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1439

2878

4318

5757

7196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.290

Hom.:

10232

Bravo

AF:

0.235

Asia WGS

AF:

0.230

AC:

802

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.313

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 12

Benign:4

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 37. Only high quality variants are reported. -

Apr 25, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 24, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Early Infantile Epileptic Encephalopathy, Autosomal Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.5

(source)

DANN

Benign

0.39

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(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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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