rs718174

Positions:

• chr6-108052051-G-A

Variant summary

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

The NM_014028.4(OSTM1):​c.616-853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,952 control chromosomes in the GnomAD database, including 14,367 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 0.41 (14367 hom., cov: 32)
• Consequence: OSTM1 NM_014028.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSTM1	NM_014028.4	c.616-853C>T		intron_variant		ENST00000193322.8	NP_054747.2
OSTM1	XM_047418679.1	c.616-853C>T		intron_variant			XP_047274635.1
OSTM1	XM_047418680.1	c.616-853C>T		intron_variant			XP_047274636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSTM1	ENST00000193322.8	c.616-853C>T		intron_variant		1	NM_014028.4	ENSP00000193322	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62102 AN: 151834 Hom.: 14331 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.409 AC: 62217 AN: 151952 Hom.: 14367 Cov.: 32 AF XY: 0.416 AC XY: 30889 AN XY: 74248

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.386

Alfa AF: 0.362 Hom.: 1664

Bravo AF: 0.429

Asia WGS AF: 0.447 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.47

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: rs718174; hg19: chr6-108373255; COSMIC: COSV51969218; COSMIC: COSV51969218;