20-8503460-T-C

Variant names:

• chr20-8503460-T-C
• rs6086473
• NM_015192.4:c.247-124834T>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.247-124834T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,928 control chromosomes in the GnomAD database, including 36,487 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 0.69 (36487 hom., cov: 31)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	NM_015192.4	MANE Select	c.247-124834T>C		intron	N/A	NP_056007.1	Q9NQ66-1
	PLCB1	NM_182734.3		c.247-124834T>C		intron	N/A	NP_877398.1	Q9NQ66-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	ENST00000338037.11	TSL:1 MANE Select	c.247-124834T>C		intron	N/A	ENSP00000338185.6	Q9NQ66-1
	PLCB1	ENST00000378637.6	TSL:1	c.247-124834T>C		intron	N/A	ENSP00000367904.2	Q9NQ66-2
	PLCB1	ENST00000378641.7	TSL:1	c.247-124834T>C		intron	N/A	ENSP00000367908.3	Q9NQ66-2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 104977 AN: 151810 Hom.: 36442 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.692 AC: 105078 AN: 151928 Hom.: 36487 Cov.: 31 AF XY: 0.687 AC XY: 50981 AN XY: 74240

African (AFR) AF: 0.698 AC: 28894 AN: 41394

American (AMR) AF: 0.698 AC: 10645 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2453 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3426 AN: 5140

South Asian (SAS) AF: 0.540 AC: 2599 AN: 4814

European-Finnish (FIN) AF: 0.681 AC: 7185 AN: 10558

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47505 AN: 67988

Other (OTH) AF: 0.712 AC: 1503 AN: 2112

Alfa AF: 0.693 Hom.: 97556

Bravo AF: 0.696

Asia WGS AF: 0.666 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.49
PhyloP100		-0.040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs6086473; hg19: chr20-8484107;