rs6118378

chr20-8905362-A-C

Variant summary

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

The ENST00000487210.5(PLCB1):c.*20-56834A>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,024 control chromosomes in the GnomAD database, including 3,693 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 0.19 (3693 hom., cov: 31)
• Consequence: PLCB1 ENST00000487210.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 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.*20-56834A>C		intron_variant, NMD_transcript_variant		1
PLCB1	ENST00000635929.1	c.593-56834A>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29264 AN: 151908 Hom.: 3696 Cov.: 31

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.192 AC: 29258 AN: 152024 Hom.: 3693 Cov.: 31 AF XY: 0.189 AC XY: 14045 AN XY: 74294

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.224

Alfa AF: 0.259 Hom.: 2555

Bravo AF: 0.182

Asia WGS AF: 0.0870 AC: 301 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	4.9
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6118378; hg19: chr20-8886009;