chr17-50201443-TCTTGGC-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5

The NM_000088.4(COL1A1):​c.65_70delGCCAAG​(p.Gly22_Gln23del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

COL1A1
NM_000088.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.01
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a signal_peptide (size 21) in uniprot entity CO1A1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_000088.4
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-50201443-TCTTGGC-T is Pathogenic according to our data. Variant chr17-50201443-TCTTGGC-T is described in ClinVar as [Pathogenic]. Clinvar id is 425636.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-50201443-TCTTGGC-T is described in Lovd as [Pathogenic]. Variant chr17-50201443-TCTTGGC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL1A1NM_000088.4 linkuse as main transcriptc.65_70delGCCAAG p.Gly22_Gln23del disruptive_inframe_deletion 1/51 ENST00000225964.10 NP_000079.2 P02452
COL1A1XM_011524341.2 linkuse as main transcriptc.65_70delGCCAAG p.Gly22_Gln23del disruptive_inframe_deletion 1/48 XP_011522643.1
COL1A1XM_005257058.5 linkuse as main transcriptc.65_70delGCCAAG p.Gly22_Gln23del disruptive_inframe_deletion 1/49 XP_005257115.2
COL1A1XM_005257059.5 linkuse as main transcriptc.65_70delGCCAAG p.Gly22_Gln23del disruptive_inframe_deletion 1/38 XP_005257116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL1A1ENST00000225964.10 linkuse as main transcriptc.65_70delGCCAAG p.Gly22_Gln23del disruptive_inframe_deletion 1/511 NM_000088.4 ENSP00000225964.6 P02452
COL1A1ENST00000474644.1 linkuse as main transcriptn.184_189delGCCAAG non_coding_transcript_exon_variant 1/43
ENSG00000249406ENST00000509943.2 linkuse as main transcriptn.59+1511_59+1516delTTGGCC intron_variant 3

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
LINK: link

Submissions by phenotype

Osteogenesis imperfecta type III Pathogenic:1
Pathogenic, no assertion criteria providedclinical testingDepartment of Medical Sciences, Uppsala University-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1114167409; hg19: chr17-48278804; API