rs747192374
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_015192.4(PLCB1):āc.1242T>Cā(p.His414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,605,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.000018 ( 0 hom. )
Consequence
PLCB1
NM_015192.4 synonymous
NM_015192.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.875
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 20-8708744-T-C is Benign according to our data. Variant chr20-8708744-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 478575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.875 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000329 (5/152206) while in subpopulation AMR AF= 0.000327 (5/15286). AF 95% confidence interval is 0.000129. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.1242T>C | p.His414= | synonymous_variant | 12/32 | ENST00000338037.11 | |
PLCB1 | NM_182734.3 | c.1242T>C | p.His414= | synonymous_variant | 12/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.1242T>C | p.His414= | synonymous_variant | 12/32 | 1 | NM_015192.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000104 AC: 26AN: 250848Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135574
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GnomAD4 exome AF: 0.0000179 AC: 26AN: 1453486Hom.: 0 Cov.: 28 AF XY: 0.0000166 AC XY: 12AN XY: 723562
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74378
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Developmental and epileptic encephalopathy, 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at