20-8714934-C-T

Position:

• chr20-8714934-C-T

Variant summary

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

The NM_015192.4(PLCB1):​c.1251-1330C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 150,260 control chromosomes in the GnomAD database, including 39,100 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 0.72 (39100 hom., cov: 31)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

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 (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.1251-1330C>T		intron_variant		ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.1251-1330C>T		intron_variant			NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.1251-1330C>T		intron_variant		1	NM_015192.4	ENSP00000338185	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 108577 AN: 150144 Hom.: 39070 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.723 AC: 108647 AN: 150260 Hom.: 39100 Cov.: 31 AF XY: 0.725 AC XY: 53188 AN XY: 73324

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.719

Alfa AF: 0.709 Hom.: 17205

Bravo AF: 0.704

Asia WGS AF: 0.713 AC: 2472 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.65

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: rs8123323; hg19: chr20-8695581;