rs1800012

Variant names:

• chr17-50200388-C-A
• rs1800012
• NM_000088.4:c.104-441G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-50200388-C-A
• chr17-50200388-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_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:5
• Conservation: PhyloP100: 1.06
• Publications: 159 publications found

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]

TILAM (HGNC:52795): (long intergenic non-protein coding RNA 1969)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-50200388-C-A is Benign according to our data. Variant chr17-50200388-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 811535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000088.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A1	NM_000088.4	MANE Select	c.104-441G>T		intron	N/A	NP_000079.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL1A1	ENST00000225964.10	TSL:1 MANE Select	c.104-441G>T		intron	N/A	ENSP00000225964.6
	COL1A1	ENST00000861334.1		c.104-441G>T		intron	N/A	ENSP00000531393.1
	COL1A1	ENST00000861339.1		c.104-441G>T		intron	N/A	ENSP00000531398.1

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

African (AFR) AF: 0.0711 AC: 2951 AN: 41508

American (AMR) AF: 0.144 AC: 2202 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3464

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5158

South Asian (SAS) AF: 0.0892 AC: 430 AN: 4820

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10608

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12635 AN: 67934

Other (OTH) AF: 0.168 AC: 354 AN: 2112

Alfa AF: 0.163 Hom.: 3340

Bravo AF: 0.134

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	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 (1)
-	-	1	not provided (1)
-	-	1	Osteogenesis imperfecta type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.1
DANN	Benign	0.68
PhyloP100		1.1
PromoterAI		0.062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800012; hg19: chr17-48277749;