chr17-50184473-CACA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000088.4(COL1A1):​c.*1026_*1028del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 171,936 control chromosomes in the GnomAD database, including 97 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.039 ( 94 hom., cov: 12)
Exomes 𝑓: 0.023 ( 3 hom. )

Consequence

COL1A1
NM_000088.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 0.507
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 -8 ACMG points.

BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL1A1NM_000088.4 linkuse as main transcriptc.*1026_*1028del 3_prime_UTR_variant 51/51 ENST00000225964.10 NP_000079.2
COL1A1XM_005257058.5 linkuse as main transcriptc.*1026_*1028del 3_prime_UTR_variant 49/49 XP_005257115.2
COL1A1XM_005257059.5 linkuse as main transcriptc.*1026_*1028del 3_prime_UTR_variant 38/38 XP_005257116.2
COL1A1XM_011524341.2 linkuse as main transcriptc.*1026_*1028del 3_prime_UTR_variant 48/48 XP_011522643.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL1A1ENST00000225964.10 linkuse as main transcriptc.*1026_*1028del 3_prime_UTR_variant 51/511 NM_000088.4 ENSP00000225964 P1

Frequencies

GnomAD3 genomes
AF:
0.0391
AC:
4246
AN:
108688
Hom.:
93
Cov.:
12
show subpopulations
Gnomad AFR
AF:
0.0100
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.0920
Gnomad ASJ
AF:
0.0374
Gnomad EAS
AF:
0.0142
Gnomad SAS
AF:
0.0271
Gnomad FIN
AF:
0.0477
Gnomad MID
AF:
0.00532
Gnomad NFE
AF:
0.0450
Gnomad OTH
AF:
0.0345
GnomAD4 exome
AF:
0.0232
AC:
1464
AN:
63220
Hom.:
3
AF XY:
0.0225
AC XY:
658
AN XY:
29194
show subpopulations
Gnomad4 AFR exome
AF:
0.00246
Gnomad4 AMR exome
AF:
0.0477
Gnomad4 ASJ exome
AF:
0.0196
Gnomad4 EAS exome
AF:
0.0217
Gnomad4 SAS exome
AF:
0.0145
Gnomad4 FIN exome
AF:
0.00641
Gnomad4 NFE exome
AF:
0.0245
Gnomad4 OTH exome
AF:
0.0244
GnomAD4 genome
AF:
0.0391
AC:
4246
AN:
108716
Hom.:
94
Cov.:
12
AF XY:
0.0397
AC XY:
2055
AN XY:
51728
show subpopulations
Gnomad4 AFR
AF:
0.0100
Gnomad4 AMR
AF:
0.0922
Gnomad4 ASJ
AF:
0.0374
Gnomad4 EAS
AF:
0.0142
Gnomad4 SAS
AF:
0.0267
Gnomad4 FIN
AF:
0.0477
Gnomad4 NFE
AF:
0.0450
Gnomad4 OTH
AF:
0.0349
Alfa
AF:
0.0339
Hom.:
0

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome type 7A Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Osteogenesis Imperfecta, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Infantile cortical hyperostosis Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 20, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs751268781; hg19: chr17-48261834; API