chr20-8757087-G-A

Position:

chr20-8757087-G-A

Variant summary

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

The NM_015192.4(PLCB1):c.2565G>A(p.Ala855=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,611,358 control chromosomes in the GnomAD database, including 71,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5232 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66464 hom. )

Consequence

PLCB1
NM_015192.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.138

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=-0.55).

BP6

Variant 20-8757087-G-A is Benign according to our data. Variant chr20-8757087-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 129908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8757087-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.138 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4 linkuse as main transcript	c.2565G>A	p.Ala855=	synonymous_variant	24/32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3 linkuse as main transcript	c.2565G>A	p.Ala855=	synonymous_variant	24/33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 linkuse as main transcript	c.2565G>A	p.Ala855=	synonymous_variant	24/32	1	NM_015192.4	ENSP00000338185	P1	Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37699

AN:

151880

Hom.:

5232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.270

AC:

67806

AN:

250748

Hom.:

9673

AF XY:

0.278

AC XY:

37677

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.298

AC:

434946

AN:

1459360

Hom.:

66464

Cov.:

AF XY:

0.300

AC XY:

217684

AN XY:

726034

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.248

AC:

37707

AN:

151998

Hom.:

5232

Cov.:

AF XY:

0.247

AC XY:

18371

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.298

Hom.:

8827

Bravo

AF:

0.235

Asia WGS

AF:

0.230

AC:

802

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.313

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 12

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 37. Only high quality variants are reported. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 24, 2020	- -

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

Jan 08, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.5

DANN

Benign

0.39

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