20-8864725-T-C

Variant names:

• chr20-8864725-T-C
• rs6108205
• NM_015192.4:c.3424-16897T>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.3424-16897T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,042 control chromosomes in the GnomAD database, including 15,345 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 0.43 (15345 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.3424-16897T>C		intron_variant	Intron 31 of 31	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.*20-16897T>C		intron_variant	Intron 32 of 32		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.3424-16897T>C		intron_variant	Intron 31 of 31	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64768 AN: 151924 Hom.: 15330 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.426 AC: 64816 AN: 152042 Hom.: 15345 Cov.: 32 AF XY: 0.431 AC XY: 32015 AN XY: 74304

African (AFR) AF: 0.225 AC: 9333 AN: 41478

American (AMR) AF: 0.532 AC: 8126 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1590 AN: 3470

East Asian (EAS) AF: 0.782 AC: 4037 AN: 5164

South Asian (SAS) AF: 0.435 AC: 2097 AN: 4816

European-Finnish (FIN) AF: 0.519 AC: 5485 AN: 10574

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32794 AN: 67956

Other (OTH) AF: 0.414 AC: 873 AN: 2110

Alfa AF: 0.467 Hom.: 10245

Bravo AF: 0.424

Asia WGS AF: 0.568 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.83
PhyloP100		-0.29
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: rs6108205; hg19: chr20-8845372;