20-8697799-G-A

Position:

• chr20-8697799-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015192.4(PLCB1):​c.1167+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,611,096 control chromosomes in the GnomAD database, including 347,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26889 hom., cov: 32)
  • Exomes 𝑓: 0.66 (320777 hom.)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0480

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-8697799-G-A is Benign according to our data. Variant chr20-8697799-G-A is described in ClinVar as [Benign]. Clinvar id is 260593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8697799-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.1167+16G>A		intron_variant		ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.1167+16G>A		intron_variant			NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.1167+16G>A		intron_variant		1	NM_015192.4	ENSP00000338185	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87783 AN: 151884 Hom.: 26886 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.608

GnomAD3 exomes AF: 0.621 AC: 155471 AN: 250230 Hom.: 50445 AF XY: 0.638 AC XY: 86292 AN XY: 135204

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.586

Gnomad SAS exome AF: 0.710

Gnomad FIN exome AF: 0.697

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.645

GnomAD4 exome AF: 0.659 AC: 961615 AN: 1459094 Hom.: 320777 Cov.: 31 AF XY: 0.663 AC XY: 480965 AN XY: 725876

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.578 AC: 87800 AN: 152002 Hom.: 26889 Cov.: 32 AF XY: 0.581 AC XY: 43197 AN XY: 74288

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.611

Alfa AF: 0.668 Hom.: 71124

Bravo AF: 0.550

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 12 Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

not specified Benign:2

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 75% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 70. Only high quality variants are reported. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 04, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2295179; hg19: chr20-8678446; COSMIC: COSV62053454;