chr9-75130508-T-C

Variant names:

• chr9-75130508-T-C
• rs2295861
• NM_012383.5:c.133-70T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 8 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSTF1	ENST00000346234.7	TSL:1 MANE Select	c.133-70T>C		intron	N/A	ENSP00000340836.6
	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.: 31

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

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

GnomAD4 genome AF: 0.771 AC: 117270 AN: 152082 Hom.: 45565 Cov.: 31 AF XY: 0.766 AC XY: 56911 AN XY: 74334

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

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
DANN	Benign	0.39
PhyloP100		-0.38
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: rs2295861; hg19: chr9-77745424; COSMIC: COSV60549284;