Genetic Variant OS9:c.340-150A>T (chr12-57695630-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006812.4(OS9):c.340-150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 722,874 control chromosomes in the GnomAD database, including 132,211 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 0.57 ( 26037 hom., cov: 31)

Exomes 𝑓: 0.60 ( 106174 hom. )

Consequence

OS9
NM_006812.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 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	UniProt
OS9	NM_006812.4	MANE Select	c.340-150A>T	intron	N/A	NP_006803.1	Q13438-1
OS9	NM_001410980.1		c.340-150A>T	intron	N/A	NP_001397909.1	A0A8V8TQI8
OS9	NM_001410978.1		c.340-150A>T	intron	N/A	NP_001397907.1	A0A8V8TR34

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OS9	ENST00000315970.12	TSL:1 MANE Select	c.340-150A>T	intron	N/A	ENSP00000318165.7	Q13438-1
OS9	ENST00000552285.6	TSL:1	c.340-150A>T	intron	N/A	ENSP00000450010.1	Q13438-2
OS9	ENST00000856494.1		c.340-150A>T	intron	N/A	ENSP00000526553.1

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87212

AN:

151804

Hom.:

26042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.628

GnomAD4 exome

AF:

0.597

AC:

340795

AN:

570950

Hom.:

106174

Cov.:

AF XY:

0.587

AC XY:

181581

AN XY:

309156

show subpopulations

African (AFR)

AF:

0.421

AC:

6741

AN:

16024

American (AMR)

AF:

0.619

AC:

21744

AN:

35128

Ashkenazi Jewish (ASJ)

AF:

0.675

AC:

13563

AN:

20082

East Asian (EAS)

AF:

0.285

AC:

9263

AN:

32542

South Asian (SAS)

AF:

0.394

AC:

25084

AN:

63650

European-Finnish (FIN)

AF:

0.612

AC:

28757

AN:

47026

Middle Eastern (MID)

AF:

0.626

AC:

2555

AN:

4084

European-Non Finnish (NFE)

AF:

0.666

AC:

214158

AN:

321450

Other (OTH)

AF:

0.611

AC:

18930

AN:

30964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

7260

14520

21779

29039

36299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.574

AC:

87234

AN:

151924

Hom.:

26037

Cov.:

AF XY:

0.567

AC XY:

42108

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.429

AC:

17761

AN:

41388

American (AMR)

AF:

0.634

AC:

9684

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

2350

AN:

3466

East Asian (EAS)

AF:

0.350

AC:

1803

AN:

5156

South Asian (SAS)

AF:

0.387

AC:

1869

AN:

4824

European-Finnish (FIN)

AF:

0.595

AC:

6279

AN:

10546

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.670

AC:

45520

AN:

67964

Other (OTH)

AF:

0.625

AC:

1313

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1789

3579

5368

7158

8947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.488

Hom.:

1418

Bravo

AF:

0.573

Asia WGS

AF:

0.388

AC:

1352

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: -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