rs2001144

Variant names:

• chr6-108086458-A-C
• rs2001144
• ENST00000699581.1:c.-40+13779T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-108086458-A-C
• chr6-108086458-A-G
• chr6-108086458-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

OSTM1 Gene-Disease associations (from GenCC):

• autosomal recessive osteopetrosis 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• infantile osteopetrosis with neuroaxonal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSTM1	ENST00000699581.1	c.-40+13779T>G		intron_variant	Intron 2 of 6			ENSP00000514455.1
OSTM1	ENST00000440575.6	c.-39-22159T>G		intron_variant	Intron 2 of 6	5		ENSP00000398556.2

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

African (AFR) AF: 0.563 AC: 23332 AN: 41474

American (AMR) AF: 0.292 AC: 4458 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1967 AN: 5156

South Asian (SAS) AF: 0.188 AC: 907 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1338 AN: 10602

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4977 AN: 68022

Other (OTH) AF: 0.216 AC: 455 AN: 2106

Alfa AF: 0.158 Hom.: 7624

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
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs2001144; hg19: chr6-108407662;