rs6039266

Positions:

• chr20-8785424-A-G
• chr20-8785424-A-T

Variant summary

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

The NM_015192.4(PLCB1):​c.3112-3025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,172 control chromosomes in the GnomAD database, including 63,012 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 0.91 (63012 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.3112-3025A>G		intron_variant		ENST00000338037.11
PLCB1	NM_182734.3	c.3112-3025A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.3112-3025A>G		intron_variant		1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137719 AN: 152054 Hom.: 62985 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.906 AC: 137799 AN: 152172 Hom.: 63012 Cov.: 32 AF XY: 0.908 AC XY: 67547 AN XY: 74396

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.943

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.939

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.962

Gnomad4 OTH AF: 0.909

Alfa AF: 0.936 Hom.: 4492

Bravo AF: 0.897

Asia WGS AF: 0.961 AC: 3340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.55

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: rs6039266; hg19: chr20-8766071;