12-57713053-A-G

Variant names:

• chr12-57713053-A-G
• rs701006
• NM_006812.4:c.580-2707A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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]

ENSG00000257342 (HGNC:58278):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OS9	NM_006812.4	MANE Select	c.580-2707A>G		intron	N/A	NP_006803.1
	OS9	NM_001410980.1		c.580-2707A>G		intron	N/A	NP_001397909.1
	OS9	NM_001410978.1		c.580-2707A>G		intron	N/A	NP_001397907.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OS9	ENST00000315970.12	TSL:1 MANE Select	c.580-2707A>G		intron	N/A	ENSP00000318165.7
	OS9	ENST00000552285.6	TSL:1	c.580-2707A>G		intron	N/A	ENSP00000450010.1
	OS9	ENST00000700665.1		c.580-2707A>G		intron	N/A	ENSP00000515134.1

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

African (AFR) AF: 0.505 AC: 20910 AN: 41408

American (AMR) AF: 0.617 AC: 9409 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1835 AN: 5164

South Asian (SAS) AF: 0.444 AC: 2137 AN: 4816

European-Finnish (FIN) AF: 0.544 AC: 5733 AN: 10540

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40626 AN: 67942

Other (OTH) AF: 0.601 AC: 1265 AN: 2104

Alfa AF: 0.587 Hom.: 76193

Bravo AF: 0.562

Asia WGS AF: 0.437 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.85
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: rs701006; hg19: chr12-58106836;