12-57713053-A-G

Position:

• chr12-57713053-A-G

Variant summary

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

The NM_006812.4(OS9):​c.580-2707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,902 control chromosomes in the GnomAD database, including 24,087 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 0.56 (24087 hom., cov: 31)
• Consequence: OS9 NM_006812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

Genes affected

OS9 (HGNC:16994): (OS9 endoplasmic reticulum lectin) This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OS9	NM_006812.4	c.580-2707A>G		intron_variant		ENST00000315970.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OS9	ENST00000315970.12	c.580-2707A>G		intron_variant		1	NM_006812.4	P4
	ENST00000549477.1	n.534+7924T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84808 AN: 151784 Hom.: 24078 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.559 AC: 84856 AN: 151902 Hom.: 24087 Cov.: 31 AF XY: 0.554 AC XY: 41104 AN XY: 74192

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.601

Alfa AF: 0.595 Hom.: 47688

Bravo AF: 0.562

Asia WGS AF: 0.437 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.54

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: rs701006; hg19: chr12-58106836;