rs2001144

Positions:

• chr6-108086458-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699581.1(OSTM1):​c.-40+13779T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,144 control chromosomes in the GnomAD database, including 8,106 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 0.25 (8106 hom., cov: 32)
• Consequence: OSTM1 ENST00000699581.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

Genes affected

OSTM1 (HGNC:21652): (osteoclastogenesis associated transmembrane protein 1) This gene encodes a protein that may be involved in the degradation of G proteins via the ubiquitin-dependent proteasome pathway. The encoded protein binds to members of subfamily A of the regulator of the G-protein signaling (RGS) family through an N-terminal leucine-rich region. This protein also has a central RING finger-like domain and E3 ubiquitin ligase activity. This protein is highly conserved from flies to humans. Defects in this gene may cause the autosomal recessive, infantile malignant form of osteopetrosis. [provided by RefSeq, Jul 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 = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSTM1	ENST00000440575.6	c.-39-22159T>G		intron_variant		5		ENSP00000398556
OSTM1	ENST00000699581.1	c.-40+13779T>G		intron_variant				ENSP00000514455

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37802 AN: 152026 Hom.: 8080 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 37898 AN: 152144 Hom.: 8106 Cov.: 32 AF XY: 0.253 AC XY: 18784 AN XY: 74384

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.216

Alfa AF: 0.114 Hom.: 2630

Bravo AF: 0.275

Asia WGS AF: 0.299 AC: 1036 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.44
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2001144; hg19: chr6-108407662;