rs3761170

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015192.4(PLCB1):c.2082G>A(p.Gly694Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 1,612,662 control chromosomes in the GnomAD database, including 4,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 410 hom., cov: 33)

Exomes 𝑓: 0.069 ( 4263 hom. )

Consequence

PLCB1
NM_015192.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.276

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 20-8737066-G-A is Benign according to our data. Variant chr20-8737066-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 129903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8737066-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.276 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4 link	c.2082G>A	p.Gly694Gly	synonymous_variant	Exon 20 of 32	ENST00000338037.11	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3 link	c.2082G>A	p.Gly694Gly	synonymous_variant	Exon 20 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.2082G>A	p.Gly694Gly	synonymous_variant	Exon 20 of 32	1	NM_015192.4	ENSP00000338185.6		Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9628

AN:

152062

Hom.:

405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0934

Gnomad ASJ

AF:

0.0978

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0629

Gnomad OTH

AF:

0.0856

GnomAD3 exomes

AF:

0.0799

AC:

20068

AN:

251248

Hom.:

980

AF XY:

0.0837

AC XY:

11361

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.0838

Gnomad ASJ exome

AF:

0.0921

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.0411

Gnomad NFE exome

AF:

0.0644

Gnomad OTH exome

AF:

0.0747

GnomAD4 exome

AF:

0.0692

AC:

101115

AN:

1460482

Hom.:

4263

Cov.:

AF XY:

0.0721

AC XY:

52391

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.0325

Gnomad4 AMR exome

AF:

0.0848

Gnomad4 ASJ exome

AF:

0.0911

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.0397

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0773

GnomAD4 genome

AF:

0.0634

AC:

9641

AN:

152180

Hom.:

410

Cov.:

AF XY:

0.0650

AC XY:

4838

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0351

Gnomad4 AMR

AF:

0.0933

Gnomad4 ASJ

AF:

0.0978

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0629

Gnomad4 OTH

AF:

0.0922

Alfa

AF:

0.0538

Hom.:

137

Bravo

AF:

0.0617

Asia WGS

AF:

0.158

AC:

549

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 24, 2020

GeneDx

Significance: 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

- -

Inborn genetic diseases

Benign:1

Mar 13, 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

-0.53

CADD

Benign

6.6

DANN

Benign

0.49

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