rs6086350

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.99+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 1,598,996 control chromosomes in the GnomAD database, including 1,616 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 164 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1452 hom. )

Consequence

PLCB1
NM_015192.4 splice_region, intron

Scores

Splicing: ADA: 0.0001641

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.06

Publications

5 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=-0.74).

BP6

Variant 20-8132758-T-C is Benign according to our data. Variant chr20-8132758-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.99+8T>C		splice_region_variant, intron_variant	Intron 1 of 31	ENST00000338037.11	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3 link	c.99+8T>C		splice_region_variant, intron_variant	Intron 1 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.99+8T>C		splice_region_variant, intron_variant	Intron 1 of 31	1	NM_015192.4	ENSP00000338185.6		Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6506

AN:

151996

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0495

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0542

GnomAD2 exomes

AF:

0.0395

AC:

9656

AN:

244594

AF XY:

0.0393

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.0366

Gnomad ASJ exome

AF:

0.0985

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0208

Gnomad NFE exome

AF:

0.0468

Gnomad OTH exome

AF:

0.0543

GnomAD4 exome

AF:

0.0412

AC:

59623

AN:

1446888

Hom.:

1452

Cov.:

AF XY:

0.0410

AC XY:

29533

AN XY:

720626

show subpopulations

African (AFR)

AF:

0.0447

AC:

1478

AN:

33096

American (AMR)

AF:

0.0388

AC:

1729

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.0971

AC:

2520

AN:

25948

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39540

South Asian (SAS)

AF:

0.0252

AC:

2164

AN:

85714

European-Finnish (FIN)

AF:

0.0228

AC:

1209

AN:

53046

Middle Eastern (MID)

AF:

0.0818

AC:

468

AN:

5718

European-Non Finnish (NFE)

AF:

0.0429

AC:

47220

AN:

1099452

Other (OTH)

AF:

0.0473

AC:

2833

AN:

59854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2835

5670

8505

11340

14175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1716

3432

5148

6864

8580

<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:

0.0428

AC:

6508

AN:

152108

Hom.:

164

Cov.:

AF XY:

0.0413

AC XY:

3074

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0447

AC:

1857

AN:

41508

American (AMR)

AF:

0.0494

AC:

755

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0893

AC:

310

AN:

3470

East Asian (EAS)

AF:

0.000390

AC:

AN:

5124

South Asian (SAS)

AF:

0.0211

AC:

102

AN:

4832

European-Finnish (FIN)

AF:

0.0176

AC:

187

AN:

10596

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0458

AC:

3111

AN:

67968

Other (OTH)

AF:

0.0532

AC:

112

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

340

679

1019

1358

1698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0483

Hom.:

150

Bravo

AF:

0.0456

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 18, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 23, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 01, 2020

GeneDx

Significance:Likely 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

- -

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

-0.74

CADD

Benign

8.2

(source)

DANN

Benign

0.82

PhyloP100

-1.1

PromoterAI

0.048

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.0

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