17-50184475-C-CA

Variant summary

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

The NM_000088.4(COL1A1):c.*1026_*1027insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 120,442 control chromosomes in the GnomAD database, including 70 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (70 hom., cov: 26)
  • Exomes 𝑓: 0.11 (0 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-C-CA is Benign according to our data. Variant chr17-50184475-C-CA is described in ClinVar as [Benign]. Clinvar id is 1257603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A1	NM_000088.4	c.*1026_*1027insT		3_prime_UTR_variant	51/51	ENST00000225964.10
COL1A1	XM_005257058.5	c.*1026_*1027insT		3_prime_UTR_variant	49/49
COL1A1	XM_005257059.5	c.*1026_*1027insT		3_prime_UTR_variant	38/38
COL1A1	XM_011524341.2	c.*1026_*1027insT		3_prime_UTR_variant	48/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10	c.*1026_*1027insT		3_prime_UTR_variant	51/51	1	NM_000088.4	P1

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 2694 AN: 72992 Hom.: 70 Cov.: 26

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.00847

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00631

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.0515

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0313

GnomAD4 exome AF: 0.105 AC: 4993 AN: 47452 Hom.: 0 Cov.: 0 AF XY: 0.105 AC XY: 2305 AN XY: 21966

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0687

Gnomad4 SAS exome AF: 0.0920

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.0369 AC: 2693 AN: 72990 Hom.: 70 Cov.: 26 AF XY: 0.0366 AC XY: 1269 AN XY: 34698

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00635

Gnomad4 SAS AF: 0.0274

Gnomad4 FIN AF: 0.00678

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0312

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 12, 2021

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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;