20-8865359-C-A

Variant names:

• chr20-8865359-C-A
• rs6516415
• NM_015192.4:c.3424-16263C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 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.3424-16263C>A		intron	N/A	NP_056007.1
	PLCB1	NM_182734.3		c.*20-16263C>A		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.3424-16263C>A		intron	N/A	ENSP00000338185.6
	PLCB1	ENST00000378641.7	TSL:1	c.*20-16263C>A		intron	N/A	ENSP00000367908.3
	PLCB1	ENST00000487210.5	TSL:1	n.*19+63186C>A		intron	N/A	ENSP00000431704.1

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

African (AFR) AF: 0.339 AC: 14055 AN: 41420

American (AMR) AF: 0.300 AC: 4590 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1150 AN: 3470

East Asian (EAS) AF: 0.143 AC: 738 AN: 5168

South Asian (SAS) AF: 0.303 AC: 1463 AN: 4826

European-Finnish (FIN) AF: 0.355 AC: 3735 AN: 10528

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23296 AN: 67964

Other (OTH) AF: 0.364 AC: 767 AN: 2108

Alfa AF: 0.336 Hom.: 11628

Bravo AF: 0.327

Asia WGS AF: 0.228 AC: 793 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.13
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: rs6516415; hg19: chr20-8846006;