rs762562905

Variant names:

• chr20-8788449-C-G
• NM_015192.4:c.3112C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-8788449-C-G
• chr20-8788449-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015192.4(PLCB1):​c.3112C>G​(p.Leu1038Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLCB1 NM_015192.4 missense, splice_region
• Scores: Splicing: ADA: 0.0007591
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3840669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.3112C>G	p.Leu1038Val	missense_variant, splice_region_variant	Exon 28 of 32	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.3112C>G	p.Leu1038Val	missense_variant, splice_region_variant	Exon 28 of 33		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.3112C>G	p.Leu1038Val	missense_variant, splice_region_variant	Exon 28 of 32	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459926 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725998

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Benign	0.27
DEOGEN2	Benign	0.21	.;.;.;T;.;T;.;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D;.;D;D;D;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;.;L;L;L;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.47	.;.;N;N;N;.;.;.
REVEL	Benign	0.073
Sift	Benign	0.42	.;.;T;T;T;.;.;.
Sift4G	Benign	0.57	.;T;T;T;T;T;T;T
Polyphen		0.21, 0.36	.;.;B;B;B;.;.;.
Vest4		0.50, 0.48, 0.50
MutPred		0.67		.;.;Gain of MoRF binding (P = 0.0797);Gain of MoRF binding (P = 0.0797);Gain of MoRF binding (P = 0.0797);.;.;.;
MVP		0.36
MPC		0.53
ClinPred		0.80	D
GERP RS		5.3
Varity_R		0.14
gMVP		0.081

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00076
dbscSNV1_RF	Benign	0.086
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: chr20-8769096;