Variant rs6086350 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:6

Conservation

PhyloP100: -1.06

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 129917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8132758-T-C is described in Lovd as [Benign].

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/exons	MANE	UniProt
PLCB1	NM_015192.4 linkuse as main transcript	c.99+8T>C		splice_region_variant, intron_variant		ENST00000338037.11
PLCB1	NM_182734.3 linkuse as main transcript	c.99+8T>C		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11 linkuse as main transcript	c.99+8T>C		splice_region_variant, intron_variant		1	NM_015192.4	P1	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

GnomAD3 exomes

AF:

0.0395

AC:

9656

AN:

244594

Hom.:

240

AF XY:

0.0393

AC XY:

5233

AN XY:

133070

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 SAS exome

AF:

0.0266

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

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.0388

Gnomad4 ASJ exome

AF:

0.0971

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0429

Gnomad4 OTH exome

AF:

0.0473

GnomAD4 genome

AF:

0.0428

AC:

6508

AN:

152108

Hom.:

164

Cov.:

AF XY:

0.0413

AC XY:

3074

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0447

Gnomad4 AMR

AF:

0.0494

Gnomad4 ASJ

AF:

0.0893

Gnomad4 EAS

AF:

0.000390

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.0176

Gnomad4 NFE

AF:

0.0458

Gnomad4 OTH

AF:

0.0532

Alfa

AF:

0.0490

Hom.:

115

Bravo

AF:

0.0456

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 23, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 18, 2013	- -

Early Infantile Epileptic Encephalopathy, Autosomal Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2020

- -

Developmental and epileptic encephalopathy, 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.2

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over