rs4816129

Positions:

• chr20-9272941-T-C

Variant summary

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

The NM_001377142.1(PLCB4):​c.-15-34859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 150,800 control chromosomes in the GnomAD database, including 23,748 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 0.52 (23748 hom., cov: 28)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.72

Genes affected

PLCB4 (HGNC:9059): (phospholipase C beta 4) 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 in the retina. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB4	NM_001377142.1	c.-15-34859T>C		intron_variant		ENST00000378473.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB4	ENST00000378473.9	c.-15-34859T>C		intron_variant		1	NM_001377142.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 78691 AN: 150690 Hom.: 23694 Cov.: 28

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 78802 AN: 150800 Hom.: 23748 Cov.: 28 AF XY: 0.528 AC XY: 38860 AN XY: 73598

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.499

Alfa AF: 0.420 Hom.: 3764

Bravo AF: 0.549

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4816129; hg19: chr20-9253588;