Genetic Variant YBX1:p.Pro15His (chr1-42682609-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004559.5(YBX1):c.44C>A(p.Pro15His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,293,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

YBX1
NM_004559.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.83

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23971897).

BS2

High AC in GnomAdExome4 at 10 AD gene.

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.44C>A	p.Pro15His	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.44C>A	p.Pro15His	missense	Exon 1 of 8	ENSP00000361626.3	P67809
YBX1	ENST00000936897.1		c.44C>A	p.Pro15His	missense	Exon 1 of 9	ENSP00000606956.1
YBX1	ENST00000886270.1		c.44C>A	p.Pro15His	missense	Exon 1 of 8	ENSP00000556329.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000773

AC:

AN:

1293536

Hom.:

Cov.:

AF XY:

0.00000943

AC XY:

AN XY:

636504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26150

American (AMR)

AF:

0.00

AC:

AN:

24726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21360

East Asian (EAS)

AF:

0.00

AC:

AN:

27794

South Asian (SAS)

AF:

0.00

AC:

AN:

68806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3758

European-Non Finnish (NFE)

AF:

0.00000965

AC:

AN:

1036012

Other (OTH)

AF:

0.00

AC:

AN:

53374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.51

M_CAP

Benign

0.028

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

PhyloP100

2.8

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.2

REVEL

Benign

0.091

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.27

MutPred

0.18

Loss of glycosylation at P15 (P = 0.005)

MVP

0.10

MPC

2.4

ClinPred

0.83

GERP RS

3.4

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.23

gMVP

0.17

Mutation Taster

=90/10

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over