rs1800012

chr17-50200388-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000088.4(COL1A1):c.104-441G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,102 control chromosomes in the GnomAD database, including 1,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.14 (1672 hom., cov: 32)
• Consequence: COL1A1 NM_000088.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.06

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A1	NM_000088.4	c.104-441G>T		intron_variant		ENST00000225964.10
COL1A1	XM_005257058.5	c.104-441G>T		intron_variant
COL1A1	XM_005257059.5	c.104-441G>T		intron_variant
COL1A1	XM_011524341.2	c.104-441G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A1	ENST00000225964.10	c.104-441G>T		intron_variant		1	NM_000088.4	P1
	ENST00000509943.2	n.59+454C>A		intron_variant, non_coding_transcript_variant		3
COL1A1	ENST00000474644.1	n.223-441G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20819 AN: 151984 Hom.: 1675 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20815 AN: 152102 Hom.: 1672 Cov.: 32 AF XY: 0.133 AC XY: 9861 AN XY: 74368

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.00233

Gnomad4 SAS AF: 0.0892

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.168

Alfa AF: 0.164 Hom.: 467

Bravo AF: 0.134

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 09, 2018

- -

Infantile cortical hyperostosis;C0023931:Osteogenesis imperfecta type I;C0029456:Osteoporosis;C0268358:Osteogenesis imperfecta, perinatal lethal;C0268362:Osteogenesis imperfecta type III;C0268363:Osteogenesis imperfecta with normal sclerae, dominant form;C4551623:Ehlers-Danlos syndrome, arthrochalasia type;C5436842:Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 06, 2022

- -

Osteogenesis imperfecta type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.1
DANN	Benign	0.68

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: rs1800012; hg19: chr17-48277749;