rs6056209

Positions:

• chr20-8856124-G-A
• chr20-8856124-G-T

Variant summary

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

The NM_015192.4(PLCB1):​c.3424-25498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,724 control chromosomes in the GnomAD database, including 18,050 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 0.48 (18050 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.3424-25498G>A		intron_variant		ENST00000338037.11
PLCB1	NM_182734.3	c.*20-25498G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.3424-25498G>A		intron_variant		1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73160 AN: 151606 Hom.: 18051 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.482 AC: 73186 AN: 151724 Hom.: 18050 Cov.: 32 AF XY: 0.480 AC XY: 35563 AN XY: 74134

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.498

Alfa AF: 0.467 Hom.: 38435

Bravo AF: 0.475

Asia WGS AF: 0.369 AC: 1284 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.49

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: rs6056209; hg19: chr20-8836771;