20-8788533-C-T

Position:

chr20-8788533-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015192.4(PLCB1):c.3188+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,611,776 control chromosomes in the GnomAD database, including 731,822 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 Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62564 hom., cov: 34)

Exomes 𝑓: 0.96 ( 669258 hom. )

Consequence

PLCB1
NM_015192.4 splice_region, intron

Scores

Splicing: ADA: 0.00008477

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.0510

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 20-8788533-C-T is Benign according to our data. Variant chr20-8788533-C-T is described in ClinVar as [Benign]. Clinvar id is 129912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8788533-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.3188+8C>T		splice_region_variant, intron_variant		ENST00000338037.11
PLCB1	NM_182734.3 linkuse as main transcript	c.3188+8C>T		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.3188+8C>T		splice_region_variant, intron_variant		1	NM_015192.4	P1	Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.902

AC:

137162

AN:

152142

Hom.:

62540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.947

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.918

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.940

Gnomad FIN

AF:

0.987

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.907

GnomAD3 exomes

AF:

0.947

AC:

235373

AN:

248588

Hom.:

111889

AF XY:

0.948

AC XY:

127314

AN XY:

134252

show subpopulations

Gnomad AFR exome

AF:

0.743

Gnomad AMR exome

AF:

0.969

Gnomad ASJ exome

AF:

0.919

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.930

Gnomad FIN exome

AF:

0.986

Gnomad NFE exome

AF:

0.961

Gnomad OTH exome

AF:

0.945

GnomAD4 exome

AF:

0.957

AC:

1396571

AN:

1459516

Hom.:

669258

Cov.:

AF XY:

0.956

AC XY:

694111

AN XY:

725930

show subpopulations

Gnomad4 AFR exome

AF:

0.738

Gnomad4 AMR exome

AF:

0.965

Gnomad4 ASJ exome

AF:

0.919

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.929

Gnomad4 FIN exome

AF:

0.983

Gnomad4 NFE exome

AF:

0.965

Gnomad4 OTH exome

AF:

0.943

GnomAD4 genome

AF:

0.901

AC:

137239

AN:

152260

Hom.:

62564

Cov.:

AF XY:

0.904

AC XY:

67293

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.918

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.940

Gnomad4 FIN

AF:

0.987

Gnomad4 NFE

AF:

0.962

Gnomad4 OTH

AF:

0.908

Alfa

AF:

0.927

Hom.:

35187

Bravo

AF:

0.892

Asia WGS

AF:

0.960

AC:

3339

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 94% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 87. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 24, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -

Developmental and epileptic encephalopathy, 12

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2020	- -

Early Infantile Epileptic Encephalopathy, Autosomal Recessive

Benign:1

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

May 31, 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

-0.79

CADD

Benign

4.5

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

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