chr1-42696753-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004559.5(YBX1):​c.466C>T​(p.Arg156Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

YBX1
NM_004559.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67
Variant links:
Genes affected
YBX1 (HGNC:8014): (Y-box binding protein 1) This gene encodes a highly conserved cold shock domain protein that has broad nucleic acid binding properties. The encoded protein functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes including regulation of transcription and translation, pre-mRNA splicing, DNA reparation and mRNA packaging. This protein is also a component of messenger ribonucleoprotein (mRNP) complexes and may have a role in microRNA processing. This protein can be secreted through non-classical pathways and functions as an extracellular mitogen. Aberrant expression of the gene is associated with cancer proliferation in numerous tissues. This gene may be a prognostic marker for poor outcome and drug resistance in certain cancers. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
YBX1NM_004559.5 linkc.466C>T p.Arg156Cys missense_variant Exon 5 of 8 ENST00000321358.12 NP_004550.2 P67809
YBX1XM_047421495.1 linkc.376C>T p.Arg126Cys missense_variant Exon 4 of 6 XP_047277451.1
YBX1NR_132737.2 linkn.466C>T non_coding_transcript_exon_variant Exon 4 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
YBX1ENST00000321358.12 linkc.466C>T p.Arg156Cys missense_variant Exon 5 of 8 1 NM_004559.5 ENSP00000361626.3 P67809
YBX1ENST00000436427.1 linkc.613C>T p.Arg205Cys missense_variant Exon 4 of 7 1 ENSP00000389639.1 H0Y449
YBX1ENST00000332220.10 linkc.376C>T p.Arg126Cys missense_variant Exon 4 of 5 5 ENSP00000405937.1 C9J5V9
YBX1ENST00000467957.1 linkn.547C>T non_coding_transcript_exon_variant Exon 4 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251080
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461568
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000144
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 01, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.466C>T (p.R156C) alteration is located in exon 5 (coding exon 5) of the YBX1 gene. This alteration results from a C to T substitution at nucleotide position 466, causing the arginine (R) at amino acid position 156 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.29
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.058
T;T
Polyphen
1.0
D;.
Vest4
0.79
MutPred
0.35
Loss of solvent accessibility (P = 0.0036);.;
MVP
0.35
MPC
1.6
ClinPred
0.93
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.78

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: rs201843615; hg19: chr1-43162424; API