rs2294597

Positions:

chr20-8790175-C-T

Variant summary

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

The NM_015192.4(PLCB1):c.3337C>T(p.Leu1113Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,600,448 control chromosomes in the GnomAD database, including 72,118 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 0.25 ( 5335 hom., cov: 33)

Exomes 𝑓: 0.30 ( 66783 hom. )

Consequence

PLCB1
NM_015192.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0007654

Clinical Significance

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

Conservation

PhyloP100: 1.43

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=-0.49).

BP6

Variant 20-8790175-C-T is Benign according to our data. Variant chr20-8790175-C-T is described in ClinVar as [Benign]. Clinvar id is 129914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8790175-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 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.3337C>T	p.Leu1113Leu	splice_region_variant, synonymous_variant	31/32	ENST00000338037.11	NP_056007.1	Q9NQ66-1
PLCB1	NM_182734.3 linkuse as main transcript	c.3337C>T	p.Leu1113Leu	splice_region_variant, synonymous_variant	31/33		NP_877398.1	Q9NQ66-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11 linkuse as main transcript	c.3337C>T	p.Leu1113Leu	splice_region_variant, synonymous_variant	31/32	1	NM_015192.4	ENSP00000338185.6		Q9NQ66-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38220

AN:

151918

Hom.:

5336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.274

AC:

67376

AN:

245544

Hom.:

9654

AF XY:

0.283

AC XY:

37557

AN XY:

132654

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.299

AC:

433600

AN:

1448412

Hom.:

66783

Cov.:

AF XY:

0.302

AC XY:

217815

AN XY:

720770

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.251

AC:

38228

AN:

152036

Hom.:

5335

Cov.:

AF XY:

0.251

AC XY:

18642

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.352

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.301

Hom.:

12935

Bravo

AF:

0.238

Asia WGS

AF:

0.259

AC:

903

AN:

3478

ClinVar

Significance: 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, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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 38% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 35. Only high quality variants are reported. -

not provided

Benign:3

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

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

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

-0.49

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00077

dbscSNV1_RF

Benign

0.19

SpliceAI score (max)

0.040

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