rs708914

Variant names:

• chr20-8421069-C-T
• rs708914
• NM_015192.4:c.246+49619C>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.246+49619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,958 control chromosomes in the GnomAD database, including 15,780 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 0.45 (15780 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 7 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

LOC124900459 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.246+49619C>T		intron_variant	Intron 3 of 31	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.246+49619C>T		intron_variant	Intron 3 of 32		NP_877398.1
LOC124900459	XR_007067518.1	n.6108-1273C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.246+49619C>T		intron_variant	Intron 3 of 31	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68892 AN: 151842 Hom.: 15769 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.454 AC: 68928 AN: 151958 Hom.: 15780 Cov.: 32 AF XY: 0.458 AC XY: 33984 AN XY: 74266

African (AFR) AF: 0.485 AC: 20117 AN: 41452

American (AMR) AF: 0.490 AC: 7474 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2218 AN: 5160

South Asian (SAS) AF: 0.509 AC: 2450 AN: 4814

European-Finnish (FIN) AF: 0.497 AC: 5251 AN: 10562

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28900 AN: 67942

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.431 Hom.: 23959

Bravo AF: 0.457

Asia WGS AF: 0.421 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.37
PhyloP100		-1.8
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: rs708914; hg19: chr20-8401716;