rs3761170

chr20-8737066-G-Achr20-8737066-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015192.4(PLCB1):c.2082G>A(p.Gly694=) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G694G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.063 (410 hom., cov: 33)
  • Exomes 𝑓: 0.069 (4263 hom.)
• Consequence: PLCB1 NM_015192.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.276

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]

ACMG classification

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/exons	MANE	UniProt
PLCB1	NM_015192.4	c.2082G>A	p.Gly694=	synonymous_variant	20/32	ENST00000338037.11
PLCB1	NM_182734.3	c.2082G>A	p.Gly694=	synonymous_variant	20/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.2082G>A	p.Gly694=	synonymous_variant	20/32	1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9628 AN: 152062 Hom.: 405 Cov.: 33

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

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.: 30 AF XY: 0.0721 AC XY: 52391 AN XY: 726610

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.: 33 AF XY: 0.0650 AC XY: 4838 AN XY: 74410

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Early Infantile Epileptic Encephalopathy, Autosomal Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2016

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 24, 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	-0.53
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

Other links and lift over

dbSNP: rs3761170; hg19: chr20-8717713;