rs4299396

Variant names:

• chr20-8934668-A-T
• rs4299396
• ENST00000487210.5:n.*20-27528A>T

Variant summary

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

The ENST00000487210.5(PLCB1):​n.*20-27528A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,140 control chromosomes in the GnomAD database, including 6,797 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 0.30 (6797 hom., cov: 33)
• Consequence: PLCB1 ENST00000487210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 4 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000487210.5	n.*20-27528A>T		intron_variant	Intron 24 of 26	1		ENSP00000431704.1
PLCB1	ENST00000635929.1	n.592-27528A>T		intron_variant	Intron 6 of 9	5		ENSP00000490792.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45136 AN: 152022 Hom.: 6796 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.297 AC: 45161 AN: 152140 Hom.: 6797 Cov.: 33 AF XY: 0.297 AC XY: 22068 AN XY: 74384

African (AFR) AF: 0.271 AC: 11252 AN: 41506

American (AMR) AF: 0.259 AC: 3957 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5184

South Asian (SAS) AF: 0.206 AC: 991 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4122 AN: 10574

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21792 AN: 67982

Other (OTH) AF: 0.270 AC: 570 AN: 2114

Alfa AF: 0.308 Hom.: 902

Bravo AF: 0.288

Asia WGS AF: 0.200 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs4299396; hg19: chr20-8915315;