chr1-204406281-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032833.5(PPP1R15B):ā€‹c.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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.561
Variant links:
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]
PPP1R15B-AS1 (HGNC:55838): (PPP1R15B and PIK3C2B antisense RNA 1)

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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
PPP1R15BNM_032833.5 linkuse as main transcriptc.1953T>C p.Tyr651= synonymous_variant 2/2 ENST00000367188.5
PPP1R15BXM_005245551.6 linkuse as main transcriptc.1920+3211T>C intron_variant
PPP1R15BXM_047432518.1 linkuse as main transcriptc.1920+3211T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP1R15BENST00000367188.5 linkuse as main transcriptc.1953T>C p.Tyr651= synonymous_variant 2/21 NM_032833.5 P1
PPP1R15B-AS1ENST00000443515.1 linkuse as main transcriptn.146+28286A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251344
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461730
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.000362
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.000132

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 08, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
6.9
DANN
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376050859; hg19: chr1-204375409; API