17-50184474-AC-A

Variant summary

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

The NM_000088.4(COL1A1):c.*1027del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000042 (0 hom., cov: 12)
  • Exomes 𝑓: 0.00015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL1A1 NM_000088.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: 0.490

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A1	NM_000088.4	c.*1027del		3_prime_UTR_variant	51/51	ENST00000225964.10
COL1A1	XM_005257058.5	c.*1027del		3_prime_UTR_variant	49/49
COL1A1	XM_005257059.5	c.*1027del		3_prime_UTR_variant	38/38
COL1A1	XM_011524341.2	c.*1027del		3_prime_UTR_variant	48/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10	c.*1027del		3_prime_UTR_variant	51/51	1	NM_000088.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 119876 Hom.: 0 Cov.: 12 FAILED QC

Gnomad AFR AF: 0.0000622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000886

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000184

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000150 AC: 10 AN: 66758 Hom.: 0 Cov.: 0 AF XY: 0.000129 AC XY: 4 AN XY: 30952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.000724

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000417 AC: 5 AN: 119926 Hom.: 0 Cov.: 12 AF XY: 0.0000515 AC XY: 3 AN XY: 58228

Gnomad4 AFR AF: 0.0000620

Gnomad4 AMR AF: 0.0000885

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000129

Gnomad4 NFE AF: 0.0000184

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome type 7A Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Osteogenesis Imperfecta, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Infantile cortical hyperostosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs878912123; hg19: chr17-48261835;