ENST00000487210.5:n.*20-56834A>C

Variant names:

• chr20-8905362-A-C
• rs6118378
• ENST00000487210.5:n.*20-56834A>C

Variant summary

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

The ENST00000487210.5(PLCB1):​n.*20-56834A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,024 control chromosomes in the GnomAD database, including 3,693 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 0.19 (3693 hom., cov: 31)
• Consequence: PLCB1 ENST00000487210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 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.*20-56834A>C		intron_variant	Intron 24 of 26	1		ENSP00000431704.1
PLCB1	ENST00000635929.1	n.592-56834A>C		intron_variant	Intron 6 of 9	5		ENSP00000490792.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29264 AN: 151908 Hom.: 3696 Cov.: 31

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.192 AC: 29258 AN: 152024 Hom.: 3693 Cov.: 31 AF XY: 0.189 AC XY: 14045 AN XY: 74294

African (AFR) AF: 0.0506 AC: 2101 AN: 41494

American (AMR) AF: 0.177 AC: 2697 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.0412 AC: 213 AN: 5176

South Asian (SAS) AF: 0.121 AC: 581 AN: 4814

European-Finnish (FIN) AF: 0.237 AC: 2494 AN: 10528

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19499 AN: 67958

Other (OTH) AF: 0.224 AC: 472 AN: 2108

Alfa AF: 0.248 Hom.: 9467

Bravo AF: 0.182

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.85
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs6118378; hg19: chr20-8886009;