12-10712155-A-G

Variant names:

• chr12-10712155-A-G
• rs812761
• NM_003651.5:c.573+1056T>C

Variant summary

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

The NM_003651.5(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 NM_003651.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003651.5. 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
	YBX3	NM_003651.5	MANE Select	c.573+1056T>C		intron	N/A	NP_003642.3
	YBX3	NM_001145426.2		c.573+1056T>C		intron	N/A	NP_001138898.1	P16989-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX3	ENST00000228251.9	TSL:1 MANE Select	c.573+1056T>C		intron	N/A	ENSP00000228251.4	P16989-1
	YBX3	ENST00000279550.11	TSL:1	c.573+1056T>C		intron	N/A	ENSP00000279550.7	P16989-2
	YBX3	ENST00000955210.1		c.573+1056T>C		intron	N/A	ENSP00000625269.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.176 AC: 7321 AN: 41496

American (AMR) AF: 0.303 AC: 4633 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1402 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1322 AN: 5176

South Asian (SAS) AF: 0.426 AC: 2045 AN: 4806

European-Finnish (FIN) AF: 0.370 AC: 3918 AN: 10578

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20210 AN: 67984

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.289 Hom.: 25017

Bravo AF: 0.259

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.55
PhyloP100		1.8
Mutation Taster		=99/1	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: rs812761; hg19: chr12-10864754;