rs2295179

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015192.4(PLCB1):c.1167+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,611,096 control chromosomes in the GnomAD database, including 347,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26889 hom., cov: 32)

Exomes 𝑓: 0.66 ( 320777 hom. )

Consequence

PLCB1
NM_015192.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0480

Publications

17 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-8697799-G-A is Benign according to our data. Variant chr20-8697799-G-A is described in ClinVar as [Benign]. Clinvar id is 260593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.1167+16G>A		intron_variant	Intron 11 of 31	ENST00000338037.11	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3 link	c.1167+16G>A		intron_variant	Intron 11 of 32		NP_877398.1	Q9NQ66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 link	c.1167+16G>A		intron_variant	Intron 11 of 31	1	NM_015192.4	ENSP00000338185.6		Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87783

AN:

151884

Hom.:

26886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.700

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.608

GnomAD2 exomes

AF:

0.621

AC:

155471

AN:

250230

AF XY:

0.638

show subpopulations

Gnomad AFR exome

AF:

0.355

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.731

Gnomad EAS exome

AF:

0.586

Gnomad FIN exome

AF:

0.697

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.645

GnomAD4 exome

AF:

0.659

AC:

961615

AN:

1459094

Hom.:

320777

Cov.:

AF XY:

0.663

AC XY:

480965

AN XY:

725876

show subpopulations

African (AFR)

AF:

0.354

AC:

11818

AN:

33402

American (AMR)

AF:

0.415

AC:

18550

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

18925

AN:

26088

East Asian (EAS)

AF:

0.561

AC:

22257

AN:

39642

South Asian (SAS)

AF:

0.707

AC:

60848

AN:

86054

European-Finnish (FIN)

AF:

0.691

AC:

36857

AN:

53362

Middle Eastern (MID)

AF:

0.699

AC:

4017

AN:

5746

European-Non Finnish (NFE)

AF:

0.675

AC:

749249

AN:

1109866

Other (OTH)

AF:

0.648

AC:

39094

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14381

28762

43143

57524

71905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19118

38236

57354

76472

95590

<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:

0.578

AC:

87800

AN:

152002

Hom.:

26889

Cov.:

AF XY:

0.581

AC XY:

43197

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.369

AC:

15303

AN:

41452

American (AMR)

AF:

0.513

AC:

7838

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

2461

AN:

3466

East Asian (EAS)

AF:

0.576

AC:

2969

AN:

5154

South Asian (SAS)

AF:

0.706

AC:

3398

AN:

4814

European-Finnish (FIN)

AF:

0.700

AC:

7398

AN:

10568

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.682

AC:

46335

AN:

67970

Other (OTH)

AF:

0.611

AC:

1288

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1761

3522

5282

7043

8804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.648

Hom.:

141253

Bravo

AF:

0.550

Asia WGS

AF:

0.622

AC:

2164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 12

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

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:2

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 75% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 70. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 04, 2019

GeneDx

Significance: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

-0.82

CADD

Benign

5.7

(source)

DANN

Benign

0.41

PhyloP100

-0.048

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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