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rs1800012

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.06
Variant links:
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]

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ACMG classification

Classification made for transcript

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
COL1A1NM_000088.4 linkuse as main transcriptc.104-441G>T intron_variant ENST00000225964.10
COL1A1XM_005257058.5 linkuse as main transcriptc.104-441G>T intron_variant
COL1A1XM_005257059.5 linkuse as main transcriptc.104-441G>T intron_variant
COL1A1XM_011524341.2 linkuse as main transcriptc.104-441G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL1A1ENST00000225964.10 linkuse as main transcriptc.104-441G>T intron_variant 1 NM_000088.4 P1
ENST00000509943.2 linkuse as main transcriptn.59+454C>A intron_variant, non_coding_transcript_variant 3
COL1A1ENST00000474644.1 linkuse as main transcriptn.223-441G>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.137
AC:
20819
AN:
151984
Hom.:
1675
Cov.:
32
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesJul 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 submitterclinical testingFulgent Genetics, Fulgent GeneticsMay 06, 2022- -
Osteogenesis imperfecta type I Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1800012; hg19: chr17-48277749; API