rs1050045

chr12-57721488-T-C

Variant summary

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

The NM_006812.4(OS9):c.*579T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,738 control chromosomes in the GnomAD database, including 12,212 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 0.40 (12164 hom., cov: 32)
  • Exomes 𝑓: 0.33 (48 hom.)
• Consequence: OS9 NM_006812.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OS9	NM_006812.4	c.*579T>C		3_prime_UTR_variant	15/15	ENST00000315970.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OS9	ENST00000315970.12	c.*579T>C		3_prime_UTR_variant	15/15	1	NM_006812.4	P4
	ENST00000549477.1	n.23A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60204 AN: 151940 Hom.: 12169 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.334 AC: 227 AN: 680 Hom.: 48 Cov.: 0 AF XY: 0.352 AC XY: 136 AN XY: 386

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.396 AC: 60217 AN: 152058 Hom.: 12164 Cov.: 32 AF XY: 0.390 AC XY: 29004 AN XY: 74346

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.455

Alfa AF: 0.442 Hom.: 15820

Bravo AF: 0.396

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.71
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1050045; hg19: chr12-58115271; COSMIC: COSV57727401; COSMIC: COSV57727401;