12-10712155-A-G

Position:

• chr12-10712155-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000228251.9(YBX3):​c.573+1056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,114 control chromosomes in the GnomAD database, including 6,158 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 0.27 (6158 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: YBX3 ENST00000228251.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

Genes affected

YBX3 (HGNC:2428): (Y-box binding protein 3) Enables RNA binding activity. Involved in cellular hyperosmotic response; cellular response to tumor necrosis factor; and negative regulation of programmed cell death. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YBX3	NM_003651.5	c.573+1056T>C		intron_variant		ENST00000228251.9	NP_003642.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YBX3	ENST00000228251.9	c.573+1056T>C		intron_variant		1	NM_003651.5	ENSP00000228251	P3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41669 AN: 151996 Hom.: 6153 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.279

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.274 AC: 41688 AN: 152114 Hom.: 6158 Cov.: 33 AF XY: 0.281 AC XY: 20916 AN XY: 74354

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.278

Alfa AF: 0.296 Hom.: 11060

Bravo AF: 0.259

Asia WGS AF: 0.300 AC: 1045 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	6.3
DANN	Benign	0.55

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: rs812761; hg19: chr12-10864754;