20-8714934-C-T

Variant names:

• chr20-8714934-C-T
• rs8123323
• NM_015192.4:c.1251-1330C>T

Variant summary

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

The NM_015192.4(PLCB1):​c.1251-1330C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 150,260 control chromosomes in the GnomAD database, including 39,100 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 0.72 (39100 hom., cov: 31)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015192.4. 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
	PLCB1	NM_015192.4	MANE Select	c.1251-1330C>T		intron	N/A	NP_056007.1
	PLCB1	NM_182734.3		c.1251-1330C>T		intron	N/A	NP_877398.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	ENST00000338037.11	TSL:1 MANE Select	c.1251-1330C>T		intron	N/A	ENSP00000338185.6
	PLCB1	ENST00000378637.6	TSL:1	c.1251-1330C>T		intron	N/A	ENSP00000367904.2
	PLCB1	ENST00000378641.7	TSL:1	c.1251-1330C>T		intron	N/A	ENSP00000367908.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 108577 AN: 150144 Hom.: 39070 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.723 AC: 108647 AN: 150260 Hom.: 39100 Cov.: 31 AF XY: 0.725 AC XY: 53188 AN XY: 73324

African (AFR) AF: 0.776 AC: 32126 AN: 41404

American (AMR) AF: 0.612 AC: 9061 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2595 AN: 3452

East Asian (EAS) AF: 0.715 AC: 3381 AN: 4730

South Asian (SAS) AF: 0.760 AC: 3633 AN: 4780

European-Finnish (FIN) AF: 0.741 AC: 7691 AN: 10382

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 47782 AN: 67416

Other (OTH) AF: 0.719 AC: 1507 AN: 2096

Alfa AF: 0.708 Hom.: 19124

Bravo AF: 0.704

Asia WGS AF: 0.713 AC: 2472 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.65
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8123323; hg19: chr20-8695581;