Genetic Variant PLCB1:n.*20-55620C>G (chr20-8906576-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000487210.5(PLCB1):n.*20-55620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,076 control chromosomes in the GnomAD database, including 14,152 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 0.42 ( 14152 hom., cov: 33)

Consequence

PLCB1
ENST00000487210.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0560

Publications

3 publications found

Variant links:

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PLCB1 links:

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new If you want to explore the variant's impact on the transcript ENST00000487210.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487210.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	ENST00000487210.5	TSL:1	n.*20-55620C>G		intron	N/A	ENSP00000431704.1	H0YCJ2
	PLCB1	ENST00000635929.1	TSL:5	n.592-55620C>G		intron	N/A	ENSP00000490792.1	A0A1B0GW62

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63769

AN:

151958

Hom.:

14151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.388

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

GnomAD4 genome

AF:

0.419

AC:

63774

AN:

152076

Hom.:

14152

Cov.:

AF XY:

0.422

AC XY:

31329

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.289

AC:

11999

AN:

41474

American (AMR)

AF:

0.446

AC:

6819

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1448

AN:

3464

East Asian (EAS)

AF:

0.233

AC:

1209

AN:

5178

South Asian (SAS)

AF:

0.362

AC:

1742

AN:

4818

European-Finnish (FIN)

AF:

0.572

AC:

6038

AN:

10564

Middle Eastern (MID)

AF:

0.349

AC:

102

AN:

292

European-Non Finnish (NFE)

AF:

0.487

AC:

33083

AN:

67988

Other (OTH)

AF:

0.385

AC:

812

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1825

3651

5476

7302

9127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.441

Hom.:

1846

Bravo

AF:

0.403

Asia WGS

AF:

0.279

AC:

972

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.6

(source)

DANN

Benign

0.70

PhyloP100

0.056

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over