rs4299396

chr20-8934668-A-T

Variant summary

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

The ENST00000487210.5(PLCB1):c.*20-27528A>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,140 control chromosomes in the GnomAD database, including 6,797 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 0.30 (6797 hom., cov: 33)
• Consequence: PLCB1 ENST00000487210.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

Genes affected

PLCB1 (HGNC:15917): (phospholipase C beta 1) 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. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000487210.5	c.*20-27528A>T		intron_variant, NMD_transcript_variant		1
PLCB1	ENST00000635929.1	c.593-27528A>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45136 AN: 152022 Hom.: 6796 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.297 AC: 45161 AN: 152140 Hom.: 6797 Cov.: 33 AF XY: 0.297 AC XY: 22068 AN XY: 74384

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.270

Alfa AF: 0.308 Hom.: 902

Bravo AF: 0.288

Asia WGS AF: 0.200 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	12
Dann	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4299396; hg19: chr20-8915315;