rs2295179

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:6
• 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	UniProt
PLCB1	NM_015192.4	c.1167+16G>A		intron_variant		ENST00000338037.11
PLCB1	NM_182734.3	c.1167+16G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.1167+16G>A		intron_variant		1	NM_015192.4	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:6

Revision: criteria provided, multiple submitters, no conflicts

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 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
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	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 2019

- -

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;