20-8132482-C-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.-170C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 354,066 control chromosomes in the GnomAD database, including 425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (148 hom., cov: 32)
  • Exomes 𝑓: 0.046 (277 hom.)
• Consequence: PLCB1 NM_015192.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.360

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=-0.64).
• BP6: Variant 20-8132482-C-A is Benign according to our data. Variant chr20-8132482-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 897294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.-170C>A		5_prime_UTR_variant	1/32	ENST00000338037.11
PLCB1	NM_182734.3	c.-170C>A		5_prime_UTR_variant	1/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.-170C>A		5_prime_UTR_variant	1/32	1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 5982 AN: 151564 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.000393

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0505

GnomAD4 exome AF: 0.0460 AC: 9320 AN: 202392 Hom.: 277 Cov.: 3 AF XY: 0.0472 AC XY: 4917 AN XY: 104156

Gnomad4 AFR exome AF: 0.0347

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.0249

Gnomad4 NFE exome AF: 0.0522

Gnomad4 OTH exome AF: 0.0525

GnomAD4 genome AF: 0.0394 AC: 5982 AN: 151674 Hom.: 148 Cov.: 32 AF XY: 0.0381 AC XY: 2828 AN XY: 74130

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.000394

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0495

Alfa AF: 0.0423 Hom.: 14

Bravo AF: 0.0417

Asia WGS AF: 0.0140 AC: 49 AN: 3446

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2020

- -

Developmental and epileptic encephalopathy, 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	10
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs139962835; hg19: chr20-8113129;