17-50184475-CA-C

Position:

• chr17-50184475-CA-C

Variant summary

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

The NM_000088.4(COL1A1):​c.*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 0.0598 in 116,802 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (2 hom., cov: 26)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: COL1A1 NM_000088.4 3_prime_UTR
• Clinical Significance: Likely 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-CA-C is Benign according to our data. Variant chr17-50184475-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1321533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A1	NM_000088.4	c.*1026del		3_prime_UTR_variant	51/51	ENST00000225964.10	NP_000079.2
COL1A1	XM_005257058.5	c.*1026del		3_prime_UTR_variant	49/49		XP_005257115.2
COL1A1	XM_005257059.5	c.*1026del		3_prime_UTR_variant	38/38		XP_005257116.2
COL1A1	XM_011524341.2	c.*1026del		3_prime_UTR_variant	48/48		XP_011522643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A1	ENST00000225964.10	c.*1026del		3_prime_UTR_variant	51/51	1	NM_000088.4	ENSP00000225964	P1

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 442 AN: 73110 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00948

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00303

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00273

Gnomad OTH AF: 0.00893

GnomAD4 exome AF: 0.150 AC: 6537 AN: 43692 Hom.: 0 Cov.: 0 AF XY: 0.150 AC XY: 3044 AN XY: 20336

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.0962

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.00606 AC: 443 AN: 73110 Hom.: 2 Cov.: 26 AF XY: 0.00647 AC XY: 225 AN XY: 34764

Gnomad4 AFR AF: 0.00966

Gnomad4 AMR AF: 0.00303

Gnomad4 ASJ AF: 0.0234

Gnomad4 EAS AF: 0.0157

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00273

Gnomad4 OTH AF: 0.00780

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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)		0.010		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: rs58879635; hg19: chr17-48261836;