9-75130508-T-C

Position:

• chr9-75130508-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSTF1	NM_012383.5	c.133-70T>C		intron_variant		ENST00000346234.7	NP_036515.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSTF1	ENST00000346234.7	c.133-70T>C		intron_variant		1	NM_012383.5	ENSP00000340836	P1

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

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.635

Gnomad4 SAS exome AF: 0.634

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.763

Gnomad4 OTH exome AF: 0.749

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

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.747

Alfa AF: 0.752 Hom.: 67345

Bravo AF: 0.772

Asia WGS AF: 0.656 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.39

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: rs2295861; hg19: chr9-77745424; COSMIC: COSV60549284;