rs17446308

Variant names:

• chr20-8718872-T-C
• rs17446308
• NM_015192.4:c.1513+1024T>C

Variant summary

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

The NM_015192.4(PLCB1):​c.1513+1024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,192 control chromosomes in the GnomAD database, including 2,700 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 (2700 hom., cov: 33)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 8 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 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.1513+1024T>C		intron	N/A	NP_056007.1
	PLCB1	NM_182734.3		c.1513+1024T>C		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.1513+1024T>C		intron	N/A	ENSP00000338185.6
	PLCB1	ENST00000378637.6	TSL:1	c.1513+1024T>C		intron	N/A	ENSP00000367904.2
	PLCB1	ENST00000378641.7	TSL:1	c.1513+1024T>C		intron	N/A	ENSP00000367908.3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28193 AN: 152074 Hom.: 2704 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.185 AC: 28202 AN: 152192 Hom.: 2700 Cov.: 33 AF XY: 0.186 AC XY: 13827 AN XY: 74406

African (AFR) AF: 0.197 AC: 8174 AN: 41510

American (AMR) AF: 0.122 AC: 1862 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5172

South Asian (SAS) AF: 0.139 AC: 669 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2319 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13376 AN: 68018

Other (OTH) AF: 0.168 AC: 356 AN: 2114

Alfa AF: 0.188 Hom.: 2307

Bravo AF: 0.179

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.83
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: rs17446308; hg19: chr20-8699519;