17-50184475-CAA-C

Position:

• chr17-50184475-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000088.4(COL1A1):​c.*1025_*1026del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 118,478 control chromosomes in the GnomAD database, including 617 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (615 hom., cov: 26)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: COL1A1 NM_000088.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 17-50184475-CAA-C is Benign according to our data. Variant chr17-50184475-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1239296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A1	NM_000088.4	c.*1025_*1026del		3_prime_UTR_variant	51/51	ENST00000225964.10
COL1A1	XM_005257058.5	c.*1025_*1026del		3_prime_UTR_variant	49/49
COL1A1	XM_005257059.5	c.*1025_*1026del		3_prime_UTR_variant	38/38
COL1A1	XM_011524341.2	c.*1025_*1026del		3_prime_UTR_variant	48/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10	c.*1025_*1026del		3_prime_UTR_variant	51/51	1	NM_000088.4	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 14691 AN: 72824 Hom.: 616 Cov.: 26

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.111 AC: 5087 AN: 45654 Hom.: 2 AF XY: 0.113 AC XY: 2394 AN XY: 21242

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.202 AC: 14689 AN: 72824 Hom.: 615 Cov.: 26 AF XY: 0.196 AC XY: 6780 AN XY: 34620

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs58879635; hg19: chr17-48261836;