20-8757172-G-C

Variant names:

• chr20-8757172-G-C
• NM_015192.4:c.2650G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015192.4(PLCB1):​c.2650G>C​(p.Ala884Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLCB1 NM_015192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06987369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.2650G>C	p.Ala884Pro	missense_variant	Exon 24 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.2650G>C	p.Ala884Pro	missense_variant	Exon 24 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.2650G>C	p.Ala884Pro	missense_variant	Exon 24 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456948 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724896

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: 9.01e-7

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	0.083
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;.;.;T;.;T;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.83	T;T;.;T;T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.070	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;.;L;L;L;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.67	.;.;N;N;N;.;.;.
REVEL	Benign	0.027
Sift	Benign	0.058	.;.;T;T;T;.;.;.
Sift4G	Benign	0.11	.;T;T;T;T;T;D;D
Polyphen		0.0010	.;.;B;B;B;.;.;.
Vest4		0.18, 0.18, 0.18
MutPred		0.17		.;.;Gain of glycosylation at A884 (P = 0.0085);Gain of glycosylation at A884 (P = 0.0085);Gain of glycosylation at A884 (P = 0.0085);.;.;.;
MVP		0.19
MPC		0.40
ClinPred		0.17	T
GERP RS		1.5
Varity_R		0.10
gMVP		0.097

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-8737819;