rs2299679

Positions:

• chr20-9428939-C-A

Variant summary

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

The NM_001377142.1(PLCB4):​c.2524+4987C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,044 control chromosomes in the GnomAD database, including 6,701 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 0.26 (6701 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.2524+4987C>A		intron_variant		ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.2524+4987C>A		intron_variant		1	NM_001377142.1	ENSP00000367734

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39735 AN: 151926 Hom.: 6675 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.262 AC: 39814 AN: 152044 Hom.: 6701 Cov.: 32 AF XY: 0.257 AC XY: 19102 AN XY: 74328

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.221

Alfa AF: 0.196 Hom.: 1923

Bravo AF: 0.284

Asia WGS AF: 0.236 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.62

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: rs2299679; hg19: chr20-9409586;