20-8427897-A-G

Variant summary

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

The NM_015192.4(PLCB1):c.246+56447A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,010 control chromosomes in the GnomAD database, including 37,061 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 0.70 (37061 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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]

LOC124900459 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.246+56447A>G		intron_variant		ENST00000338037.11
LOC124900459	XR_007067518.1	n.11663A>G		non_coding_transcript_exon_variant	2/2
PLCB1	NM_182734.3	c.246+56447A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.246+56447A>G		intron_variant		1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105813 AN: 151890 Hom.: 37006 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.697 AC: 105925 AN: 152010 Hom.: 37061 Cov.: 32 AF XY: 0.691 AC XY: 51319 AN XY: 74268

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.718

Alfa AF: 0.704 Hom.: 17255

Bravo AF: 0.693

Asia WGS AF: 0.676 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.8
Dann	Benign	0.83

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: rs2719795; hg19: chr20-8408544;