rs6516415

chr20-8865359-C-Achr20-8865359-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.3424-16263C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,978 control chromosomes in the GnomAD database, including 8,486 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 0.33 (8486 hom., cov: 33)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.3424-16263C>A		intron_variant		ENST00000338037.11
PLCB1	NM_182734.3	c.*20-16263C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.3424-16263C>A		intron_variant		1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50311 AN: 151860 Hom.: 8485 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.331 AC: 50328 AN: 151978 Hom.: 8486 Cov.: 33 AF XY: 0.331 AC XY: 24559 AN XY: 74280

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.364

Alfa AF: 0.335 Hom.: 8943

Bravo AF: 0.327

Asia WGS AF: 0.228 AC: 793 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.44

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: rs6516415; hg19: chr20-8846006;