rs1869901

chr15-40303426-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004573.3(PLCB2):c.163-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,113,060 control chromosomes in the GnomAD database, including 232,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27953 hom., cov: 30)
  • Exomes 𝑓: 0.65 (204103 hom.)
• Consequence: PLCB2 NM_004573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

Genes affected

PLCB2 (HGNC:9055): (phospholipase C beta 2) The protein encoded by this gene is a phosphodiesterase that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. The encoded protein is activated by G proteins and has been shown to be involved in the type 2 taste receptor signal transduction pathway. In addition, nuclear factor kappa B can regulate the transcription of this gene, whose protein product is also an important regulator of platelet responses. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB2	NM_004573.3	c.163-70C>T		intron_variant		ENST00000260402.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB2	ENST00000260402.8	c.163-70C>T		intron_variant		2	NM_004573.3	P4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91318 AN: 151698 Hom.: 27925 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.650 AC: 625050 AN: 961244 Hom.: 204103 AF XY: 0.649 AC XY: 323725 AN XY: 499020

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.770

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.602 AC: 91397 AN: 151816 Hom.: 27953 Cov.: 30 AF XY: 0.610 AC XY: 45257 AN XY: 74182

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.598

Alfa AF: 0.603 Hom.: 60627

Bravo AF: 0.600

Asia WGS AF: 0.724 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.6
Dann	Benign	0.67

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: rs1869901; hg19: chr15-40595627;