20-8906576-C-G

Variant names:

• chr20-8906576-C-G
• rs6140791
• ENST00000487210.5:n.*20-55620C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487210.5(PLCB1):​n.*20-55620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,076 control chromosomes in the GnomAD database, including 14,152 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 0.42 (14152 hom., cov: 33)
• Consequence: PLCB1 ENST00000487210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 3 publications found

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]

PLCB1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 12

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	ENST00000487210.5	TSL:1	n.*20-55620C>G		intron	N/A	ENSP00000431704.1
	PLCB1	ENST00000635929.1	TSL:5	n.592-55620C>G		intron	N/A	ENSP00000490792.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63769 AN: 151958 Hom.: 14151 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.419 AC: 63774 AN: 152076 Hom.: 14152 Cov.: 33 AF XY: 0.422 AC XY: 31329 AN XY: 74324

African (AFR) AF: 0.289 AC: 11999 AN: 41474

American (AMR) AF: 0.446 AC: 6819 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1448 AN: 3464

East Asian (EAS) AF: 0.233 AC: 1209 AN: 5178

South Asian (SAS) AF: 0.362 AC: 1742 AN: 4818

European-Finnish (FIN) AF: 0.572 AC: 6038 AN: 10564

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33083 AN: 67988

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.441 Hom.: 1846

Bravo AF: 0.403

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		0.056

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6140791; hg19: chr20-8887223;