17-50199933-AGGTGATT-A

Variant names:

• chr17-50199933-AGGTGATT-A
• rs1114167384
• NM_000088.4:c.111_117delAATCACC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000088.4(COL1A1):​c.111_117delAATCACC​(p.Ile38AlafsTer34) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL1A1 NM_000088.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.49
• Publications: 1 publications found

Genes affected

COL1A1 (HGNC:2197): (collagen type I alpha 1 chain) This gene encodes the pro-alpha1 chains of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

TILAM (HGNC:52795): (long intergenic non-protein coding RNA 1969)

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-50199933-AGGTGATT-A is Pathogenic according to our data. Variant chr17-50199933-AGGTGATT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 425595.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000088.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A1	NM_000088.4	MANE Select	c.111_117delAATCACC	p.Ile38AlafsTer34	frameshift	Exon 2 of 51	NP_000079.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A1	ENST00000225964.10	TSL:1 MANE Select	c.111_117delAATCACC	p.Ile38AlafsTer34	frameshift	Exon 2 of 51	ENSP00000225964.6
	COL1A1	ENST00000507689.1	TSL:2	c.165_171delAATCACC	p.Ile56AlafsTer34	frameshift	Exon 1 of 4	ENSP00000460459.1
	COL1A1	ENST00000474644.1	TSL:3	n.230_236delAATCACC		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Osteogenesis imperfecta type I Pathogenic:1

Department of Medical Sciences, Uppsala University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1114167384; hg19: chr17-48277294;