dbSNP rs1050045: OS9:c.*579T>C (chr12-57721488-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.780

Publications

31 publications found

Variant links:

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]

OS9 links:

OS9-AS1 (HGNC:58278):

OS9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OS9	NM_006812.4	MANE Select	c.*579T>C	3_prime_UTR	Exon 15 of 15	NP_006803.1
OS9	NM_001410980.1		c.*579T>C	3_prime_UTR	Exon 15 of 15	NP_001397909.1
OS9	NM_001410978.1		c.*579T>C	3_prime_UTR	Exon 15 of 15	NP_001397907.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OS9	ENST00000315970.12	TSL:1 MANE Select	c.*579T>C	3_prime_UTR	Exon 15 of 15	ENSP00000318165.7
OS9	ENST00000552285.6	TSL:1	c.*579T>C	3_prime_UTR	Exon 14 of 14	ENSP00000450010.1
OS9	ENST00000856494.1		c.*579T>C	3_prime_UTR	Exon 15 of 15	ENSP00000526553.1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60204

AN:

151940

Hom.:

12169

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.352

AC XY:

136

AN XY:

386

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.202

AC:

AN:

124

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.369

AC:

169

AN:

458

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.396

AC:

60217

AN:

152058

Hom.:

12164

Cov.:

AF XY:

0.390

AC XY:

29004

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.359

AC:

14869

AN:

41472

American (AMR)

AF:

0.377

AC:

5754

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1926

AN:

3466

East Asian (EAS)

AF:

0.231

AC:

1194

AN:

5178

South Asian (SAS)

AF:

0.311

AC:

1500

AN:

4826

European-Finnish (FIN)

AF:

0.343

AC:

3628

AN:

10580

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.440

AC:

29891

AN:

67954

Other (OTH)

AF:

0.455

AC:

961

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1854

3709

5563

7418

9272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.437

Hom.:

19879

Bravo

AF:

0.396

Asia WGS

AF:

0.305

AC:

1061

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.71

(source)

DANN

Benign

0.64

PhyloP100

-0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over