Genetic Variant OSTF1:c.133-70T>C (chr9-75130508-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_012383.5(OSTF1):c.133-70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,009,252 control chromosomes in the GnomAD database, including 282,359 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 0.77 ( 45565 hom., cov: 31)

Exomes 𝑓: 0.74 ( 236794 hom. )

Consequence

OSTF1
NM_012383.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.376

Publications

8 publications found

Variant links:

Genes affected

OSTF1 (HGNC:8510): (osteoclast stimulating factor 1) Osteoclast-stimulating factor-1 is an intracellular protein produced by osteoclasts that indirectly induces osteoclast formation and bone resorption (Reddy et al., 1998 [PubMed 10092216]).[supplied by OMIM, Mar 2008]

OSTF1 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSTF1	NM_012383.5	MANE Select	c.133-70T>C		intron	N/A	NP_036515.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OSTF1	ENST00000346234.7	TSL:1 MANE Select	c.133-70T>C	intron	N/A	ENSP00000340836.6	Q92882
OSTF1	ENST00000857346.1		c.181-70T>C	intron	N/A	ENSP00000527405.1
OSTF1	ENST00000857342.1		c.142-70T>C	intron	N/A	ENSP00000527401.1

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117161

AN:

151964

Hom.:

45509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.864

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.759

Gnomad OTH

AF:

0.748

GnomAD4 exome

AF:

0.741

AC:

634884

AN:

857170

Hom.:

236794

AF XY:

0.735

AC XY:

331497

AN XY:

450928

show subpopulations

African (AFR)

AF:

0.871

AC:

18992

AN:

21814

American (AMR)

AF:

0.681

AC:

29651

AN:

43528

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

15333

AN:

22240

East Asian (EAS)

AF:

0.635

AC:

23375

AN:

36802

South Asian (SAS)

AF:

0.634

AC:

46783

AN:

73736

European-Finnish (FIN)

AF:

0.731

AC:

38473

AN:

52616

Middle Eastern (MID)

AF:

0.743

AC:

3387

AN:

4556

European-Non Finnish (NFE)

AF:

0.763

AC:

428527

AN:

561316

Other (OTH)

AF:

0.749

AC:

30363

AN:

40562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

8095

16190

24284

32379

40474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6668

13336

20004

26672

33340

<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:

0.771

AC:

117270

AN:

152082

Hom.:

45565

Cov.:

AF XY:

0.766

AC XY:

56911

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.864

AC:

35852

AN:

41504

American (AMR)

AF:

0.708

AC:

10816

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2413

AN:

3472

East Asian (EAS)

AF:

0.646

AC:

3340

AN:

5172

South Asian (SAS)

AF:

0.619

AC:

2983

AN:

4820

European-Finnish (FIN)

AF:

0.729

AC:

7700

AN:

10566

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.760

AC:

51614

AN:

67956

Other (OTH)

AF:

0.747

AC:

1578

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1346

2692

4037

5383

6729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.760

Hom.:

154515

Bravo

AF:

0.772

Asia WGS

AF:

0.656

AC:

2279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.3

(source)

DANN

Benign

0.39

PhyloP100

-0.38

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