20-8150296-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015192.4(PLCB1):c.102C>T(p.Asp34Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,427,118 control chromosomes in the GnomAD database, including 17,701 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2571 hom., cov: 32)

Exomes 𝑓: 0.15 ( 15130 hom. )

Consequence

PLCB1
NM_015192.4 splice_region, synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.640

Publications

22 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 20-8150296-C-T is Benign according to our data. Variant chr20-8150296-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.102C>T	p.Asp34Asp	splice_region_variant, synonymous_variant	Exon 2 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3 link	c.102C>T	p.Asp34Asp	splice_region_variant, synonymous_variant	Exon 2 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 link	c.102C>T	p.Asp34Asp	splice_region_variant, synonymous_variant	Exon 2 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27307

AN:

151958

Hom.:

2569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.159

AC:

37044

AN:

233688

AF XY:

0.160

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.0893

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.150

AC:

191641

AN:

1275042

Hom.:

15130

Cov.:

AF XY:

0.153

AC XY:

98681

AN XY:

642920

show subpopulations

African (AFR)

AF:

0.212

AC:

6108

AN:

28770

American (AMR)

AF:

0.0924

AC:

3603

AN:

38978

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2751

AN:

24460

East Asian (EAS)

AF:

0.180

AC:

6819

AN:

37944

South Asian (SAS)

AF:

0.189

AC:

14735

AN:

78100

European-Finnish (FIN)

AF:

0.166

AC:

8780

AN:

52828

Middle Eastern (MID)

AF:

0.117

AC:

629

AN:

5370

European-Non Finnish (NFE)

AF:

0.147

AC:

140401

AN:

954736

Other (OTH)

AF:

0.145

AC:

7815

AN:

53856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

6005

12009

18014

24018

30023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4440

8880

13320

17760

22200

<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:

0.180

AC:

27327

AN:

152076

Hom.:

2571

Cov.:

AF XY:

0.177

AC XY:

13124

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.230

AC:

9562

AN:

41492

American (AMR)

AF:

0.114

AC:

1740

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

403

AN:

3470

East Asian (EAS)

AF:

0.148

AC:

766

AN:

5178

South Asian (SAS)

AF:

0.207

AC:

996

AN:

4818

European-Finnish (FIN)

AF:

0.154

AC:

1633

AN:

10586

Middle Eastern (MID)

AF:

0.110

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.173

AC:

11733

AN:

67920

Other (OTH)

AF:

0.156

AC:

329

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1124

2248

3372

4496

5620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.171

Hom.:

3907

Bravo

AF:

0.175

Asia WGS

AF:

0.154

AC:

533

AN:

3466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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 22% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 20. Only high quality variants are reported. -

not provided

Benign:2

Nov 20, 2020

GeneDx

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

- -

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. -

Developmental and epileptic encephalopathy, 12

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.36

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

0.64

PromoterAI

0.0032

Neutral

(source)

Mutation Taster

=97/3

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