1-42692759-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004559.5(YBX1):​c.231-731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000092 in 152,158 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.

• Frequency: Genomes: 𝑓 0.000092 (0 hom., cov: 33)
• Consequence: YBX1 NM_004559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX1	NM_004559.5	c.231-731C>T		intron_variant	Intron 2 of 7	ENST00000321358.12	NP_004550.2
YBX1	XM_047421495.1	c.231-731C>T		intron_variant	Intron 2 of 5		XP_047277451.1
YBX1	NR_132737.2	n.231-731C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX1	ENST00000321358.12	c.231-731C>T		intron_variant	Intron 2 of 7	1	NM_004559.5	ENSP00000361626.3
YBX1	ENST00000436427.1	c.378-731C>T		intron_variant	Intron 1 of 6	1		ENSP00000389639.1
YBX1	ENST00000332220.10	c.231-731C>T		intron_variant	Intron 2 of 4	5		ENSP00000405937.1
YBX1	ENST00000467957.1	n.312-731C>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152040 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

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: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74376

Gnomad4 AFR AF: 0.000313

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: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.95

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

Other links and lift over

dbSNP: rs10493112; hg19: chr1-43158430;