rs10493112

Variant names:

• chr1-42692759-C-A
• rs10493112
• NM_004559.5:c.231-731C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-42692759-C-A
• chr1-42692759-C-G
• chr1-42692759-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004559.5(YBX1):​c.231-731C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,092 control chromosomes in the GnomAD database, including 18,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18562 hom., cov: 33)
• Consequence: YBX1 NM_004559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

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.231-731C>A		intron	N/A	NP_004550.2
	YBX1	NR_132737.2		n.231-731C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX1	ENST00000321358.12	TSL:1 MANE Select	c.231-731C>A		intron	N/A	ENSP00000361626.3	P67809
	YBX1	ENST00000436427.1	TSL:1	c.378-731C>A		intron	N/A	ENSP00000389639.1	H0Y449
	YBX1	ENST00000936897.1		c.335+408C>A		intron	N/A	ENSP00000606956.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74574 AN: 151974 Hom.: 18545 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.491 AC: 74632 AN: 152092 Hom.: 18562 Cov.: 33 AF XY: 0.492 AC XY: 36559 AN XY: 74338

African (AFR) AF: 0.542 AC: 22483 AN: 41502

American (AMR) AF: 0.467 AC: 7137 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1764 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5170

South Asian (SAS) AF: 0.434 AC: 2093 AN: 4820

European-Finnish (FIN) AF: 0.536 AC: 5659 AN: 10554

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32340 AN: 67976

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.401 Hom.: 1598

Bravo AF: 0.491

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.081
DANN	Benign	0.46
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10493112;

hg19: chr1-43158430;