rs6118611

Positions:

• chr20-9433994-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.2525-1566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,132 control chromosomes in the GnomAD database, including 888 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 0.10 (888 hom., cov: 33)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.2525-1566G>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.2525-1566G>A		intron_variant		1	NM_001377142.1	ENSP00000367734

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15948 AN: 152014 Hom.: 888 Cov.: 33

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0846

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

GnomAD4 genome AF: 0.105 AC: 15945 AN: 152132 Hom.: 888 Cov.: 33 AF XY: 0.105 AC XY: 7798 AN XY: 74388

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.124 Hom.: 545

Bravo AF: 0.0970

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.57

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: rs6118611; hg19: chr20-9414641;