rs2299676

Positions:

• chr20-9376790-G-A

Variant summary

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

The NM_001377142.1(PLCB4):​c.745-3264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,984 control chromosomes in the GnomAD database, including 8,700 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 0.28 (8700 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB4	NM_001377142.1	c.745-3264G>A		intron_variant		ENST00000378473.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB4	ENST00000378473.9	c.745-3264G>A		intron_variant		1	NM_001377142.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42214 AN: 151868 Hom.: 8667 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.278 AC: 42304 AN: 151984 Hom.: 8700 Cov.: 32 AF XY: 0.275 AC XY: 20439 AN XY: 74276

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.244

Alfa AF: 0.161 Hom.: 2826

Bravo AF: 0.303

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.31

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: rs2299676; hg19: chr20-9357437;