rs6118591

Positions:

• chr20-9393873-T-C

Variant summary

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

The ENST00000378473.9(PLCB4):​c.1414+195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,958 control chromosomes in the GnomAD database, including 7,489 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 0.31 (7489 hom., cov: 32)
• Consequence: PLCB4 ENST00000378473.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.1414+195T>C		intron_variant		ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.1414+195T>C		intron_variant		1	NM_001377142.1	ENSP00000367734

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47358 AN: 151842 Hom.: 7479 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.312 AC: 47388 AN: 151958 Hom.: 7489 Cov.: 32 AF XY: 0.311 AC XY: 23094 AN XY: 74282

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.302

Alfa AF: 0.300 Hom.: 6553

Bravo AF: 0.320

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.81

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: rs6118591; hg19: chr20-9374520;