20-8132693-G-A

Variant names:

• chr20-8132693-G-A
• rs775655063
• NM_015192.4:c.42G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2 BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_015192.4(PLCB1):​c.42G>A​(p.Lys14Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PLCB1 NM_015192.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.53

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 -13 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 20-8132693-G-A is Benign according to our data. Variant chr20-8132693-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 698239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.53 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000116 (17/1460742) while in subpopulation AMR AF= 0.000269 (12/44676). AF 95% confidence interval is 0.000155. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.42G>A	p.Lys14Lys	synonymous_variant	Exon 1 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.42G>A	p.Lys14Lys	synonymous_variant	Exon 1 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.42G>A	p.Lys14Lys	synonymous_variant	Exon 1 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000403 AC: 10 AN: 248406 Hom.: 0 AF XY: 0.0000371 AC XY: 5 AN XY: 134880

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460742 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726738

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Apr 22, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

PLCB1-related disorder Benign:1

Mar 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Developmental and epileptic encephalopathy, 12 Benign:1

Oct 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs775655063; hg19: chr20-8113340;