rs16994453

chr20-8150296-C-Achr20-8150296-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_015192.4(PLCB1):c.102C>A(p.Asp34Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D34D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLCB1 NM_015192.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640

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 Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PLCB1
• BP4: Computational evidence support a benign effect (MetaRNN=0.20247781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.102C>A	p.Asp34Glu	missense_variant, splice_region_variant	2/32	ENST00000338037.11
PLCB1	NM_182734.3	c.102C>A	p.Asp34Glu	missense_variant, splice_region_variant	2/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.102C>A	p.Asp34Glu	missense_variant, splice_region_variant	2/32	1	NM_015192.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1282140 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 646222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	17
Dann	Benign	0.63
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.78	N;N;.;.;N
MutationTaster	Benign	0.073	P;P;P
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.34	N;N;.;.;N
REVEL	Benign	0.16
Sift	Benign	0.83	T;T;.;.;T
Sift4G	Benign	0.81	T;T;T;T;T
Polyphen		0.28	B;B;.;.;B
Vest4		0.40
MutPred		0.36		Loss of ubiquitination at K30 (P = 0.0795);Loss of ubiquitination at K30 (P = 0.0795);Loss of ubiquitination at K30 (P = 0.0795);Loss of ubiquitination at K30 (P = 0.0795);Loss of ubiquitination at K30 (P = 0.0795);
MVP		0.55
MPC		0.15
ClinPred		0.14	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.29

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: rs16994453; hg19: chr20-8130943;