rs143755415
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The ENST00000338037.11(PLCB1):āc.1761A>Gā(p.Val587=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000878 in 1,525,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000338037.11 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCB1 | NM_015192.4 | c.1761A>G | p.Val587= | splice_region_variant, synonymous_variant | 17/32 | ENST00000338037.11 | NP_056007.1 | |
PLCB1 | NM_182734.3 | c.1761A>G | p.Val587= | splice_region_variant, synonymous_variant | 17/33 | NP_877398.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCB1 | ENST00000338037.11 | c.1761A>G | p.Val587= | splice_region_variant, synonymous_variant | 17/32 | 1 | NM_015192.4 | ENSP00000338185 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000185 AC: 46AN: 248234Hom.: 0 AF XY: 0.000179 AC XY: 24AN XY: 134126
GnomAD4 exome AF: 0.0000844 AC: 116AN: 1373618Hom.: 0 Cov.: 21 AF XY: 0.0000857 AC XY: 59AN XY: 688220
GnomAD4 genome AF: 0.000118 AC: 18AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74326
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 12 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 31, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at