rs12030724

Variant names:

• chr1-42694347-A-T
• rs12030724
• NM_004559.5:c.264+824A>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.264+824A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 152,264 control chromosomes in the GnomAD database, including 1,007 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 0.094 (1007 hom., cov: 32)
• Consequence: YBX1 NM_004559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX1	NM_004559.5	c.264+824A>T		intron_variant	Intron 3 of 7	ENST00000321358.12	NP_004550.2
YBX1	NR_132737.2	n.264+824A>T		intron_variant	Intron 2 of 6
YBX1	XM_047421495.1	c.264+824A>T		intron_variant	Intron 3 of 5		XP_047277451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX1	ENST00000321358.12	c.264+824A>T		intron_variant	Intron 3 of 7	1	NM_004559.5	ENSP00000361626.3
YBX1	ENST00000436427.1	c.411+824A>T		intron_variant	Intron 2 of 6	1		ENSP00000389639.1
YBX1	ENST00000332220.10	c.264+824A>T		intron_variant	Intron 3 of 4	5		ENSP00000405937.1
YBX1	ENST00000467957.1	n.345+824A>T		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14332 AN: 152146 Hom.: 1005 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0942 AC: 14338 AN: 152264 Hom.: 1007 Cov.: 32 AF XY: 0.0945 AC XY: 7038 AN XY: 74460

African (AFR) AF: 0.0271 AC: 1127 AN: 41566

American (AMR) AF: 0.0855 AC: 1307 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1519 AN: 5186

South Asian (SAS) AF: 0.213 AC: 1030 AN: 4830

European-Finnish (FIN) AF: 0.0479 AC: 508 AN: 10600

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7933 AN: 68008

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0925 Hom.: 98

Bravo AF: 0.0932

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		0.052
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

Other links and lift over

dbSNP: rs12030724; hg19: chr1-43160018;