rs142813933

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015192.4(PLCB1):c.2673T>G(p.Pro891Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,610,098 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 3 hom. )

Consequence

PLCB1
NM_015192.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.233

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 20-8760423-T-G is Benign according to our data. Variant chr20-8760423-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 436321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8760423-T-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.233 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00232 (353/152316) while in subpopulation AFR AF= 0.00806 (335/41570). AF 95% confidence interval is 0.00735. There are 0 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.2673T>G	p.Pro891Pro	synonymous_variant	Exon 25 of 32	ENST00000338037.11	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3 link	c.2673T>G	p.Pro891Pro	synonymous_variant	Exon 25 of 33		NP_877398.1	Q9NQ66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 link	c.2673T>G	p.Pro891Pro	synonymous_variant	Exon 25 of 32	1	NM_015192.4	ENSP00000338185.6		Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

350

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00803

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000558

AC:

140

AN:

250856

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.00727

Gnomad AMR exome

AF:

0.000494

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000258

AC:

376

AN:

1457782

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

183

AN XY:

725336

show subpopulations

Gnomad4 AFR exome

AF:

0.00898

Gnomad4 AMR exome

AF:

0.000605

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.000548

GnomAD4 genome

AF:

0.00232

AC:

353

AN:

152316

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00806

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLCB1: BP4, BP7 -

Dec 08, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 12

Benign:2

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

Jun 10, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jun 22, 2017

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. -

PLCB1-related disorder

Benign:1

Apr 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.7

DANN

Benign

0.77

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

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