1-42682721-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004559.5(YBX1):c.156G>C(p.Lys52Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000482 in 1,244,666 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K52R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

YBX1
NM_004559.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Publications

0 publications found

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]

YBX1 links:

ENSG00000285728 (HGNC:):

ENSG00000285728 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3679273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004559.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX1	NM_004559.5	MANE Select	c.156G>C	p.Lys52Asn	missense	Exon 1 of 8	NP_004550.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YBX1	ENST00000321358.12	TSL:1 MANE Select	c.156G>C	p.Lys52Asn	missense	Exon 1 of 8	ENSP00000361626.3	P67809
YBX1	ENST00000936897.1		c.156G>C	p.Lys52Asn	missense	Exon 1 of 9	ENSP00000606956.1
YBX1	ENST00000886270.1		c.156G>C	p.Lys52Asn	missense	Exon 1 of 8	ENSP00000556329.1

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

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

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1093552

Hom.:

Cov.:

AF XY:

0.00000383

AC XY:

AN XY:

522552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22156

American (AMR)

AF:

0.00

AC:

AN:

7714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13486

East Asian (EAS)

AF:

0.00

AC:

AN:

24706

South Asian (SAS)

AF:

0.00

AC:

AN:

24956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2870

European-Non Finnish (NFE)

AF:

0.00000215

AC:

AN:

932122

Other (OTH)

AF:

0.00

AC:

AN:

43516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151114

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73774

show subpopulations

African (AFR)

AF:

0.0000968

AC:

AN:

41322

American (AMR)

AF:

0.00

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67652

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.0094

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

PhyloP100

5.2

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.18

Sift

Uncertain

0.0010

Sift4G

Benign

0.097

Polyphen

0.15

Vest4

0.23

MutPred

0.44

Loss of methylation at K52 (P = 0.007)

MVP

0.14

MPC

1.4

ClinPred

0.98

GERP RS

3.9

PromoterAI

0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.43

Mutation Taster

=48/52

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over