chr1-204406281-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_032833.5(PPP1R15B):āc.1953T>Cā(p.Tyr651=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,914 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 ).
Frequency
Genomes: š 0.000099 ( 0 hom., cov: 32)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
PPP1R15B
NM_032833.5 synonymous
NM_032833.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.561
Genes affected
PPP1R15B (HGNC:14951): (protein phosphatase 1 regulatory subunit 15B) This gene encodes a protein phosphatase I-interacting protein that promotes the dephosphorylation of eukaryotic translation initiation factor 2A to regulate translation under conditions of cellular stress. The transcribed messenger RNA contains two upstream open reading frames (ORFs) that repress translation of the main protein coding ORF under normal conditions, while the protein coding ORF is expressed at high levels in response to stress. Continual translation of the mRNA under conditions of eukaryotic translation initiation factor 2A inactivation is thought to create a feedback loop for reactivation of the gene during recovery from stress. In addition, it has been shown that this protein plays a role in membrane traffic that is independent of translation and that it is required for exocytosis from erythroleukemia cells. Allelic variants of this gene are associated with microcephaly, short stature, and impaired glucose metabolism. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 1-204406281-A-G is Benign according to our data. Variant chr1-204406281-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1974664.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.561 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP1R15B | NM_032833.5 | c.1953T>C | p.Tyr651= | synonymous_variant | 2/2 | ENST00000367188.5 | |
PPP1R15B | XM_005245551.6 | c.1920+3211T>C | intron_variant | ||||
PPP1R15B | XM_047432518.1 | c.1920+3211T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP1R15B | ENST00000367188.5 | c.1953T>C | p.Tyr651= | synonymous_variant | 2/2 | 1 | NM_032833.5 | P1 | |
PPP1R15B-AS1 | ENST00000443515.1 | n.146+28286A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251344Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135844
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461730Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727174
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74354
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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