20-9338200-G-A

Position:

• chr20-9338200-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377142.1(PLCB4):​c.225+133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 648,730 control chromosomes in the GnomAD database, including 1,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (365 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1042 hom.)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.508

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]

PLCB4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-9338200-G-A is Benign according to our data. Variant chr20-9338200-G-A is described in ClinVar as [Benign]. Clinvar id is 1244492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.225+133G>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.225+133G>A		intron_variant		1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10195 AN: 152102 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0575

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0602 AC: 29877 AN: 496510 Hom.: 1042 AF XY: 0.0610 AC XY: 16024 AN XY: 262616

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.0421

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.000130

Gnomad4 SAS exome AF: 0.0663

Gnomad4 FIN exome AF: 0.0555

Gnomad4 NFE exome AF: 0.0638

Gnomad4 OTH exome AF: 0.0673

GnomAD4 genome AF: 0.0670 AC: 10195 AN: 152220 Hom.: 365 Cov.: 32 AF XY: 0.0665 AC XY: 4952 AN XY: 74412

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.0579

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.0556

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0644 Hom.: 64

Bravo AF: 0.0694

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.21

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: rs34265063; hg19: chr20-9318847;