rs41316725

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000225964.10(COL1A1):ā€‹c.4281T>Cā€‹(p.Ile1427=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,613,940 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0040 ( 4 hom., cov: 29)
Exomes š‘“: 0.00037 ( 5 hom. )

Consequence

COL1A1
ENST00000225964.10 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0870
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 17-50185616-A-G is Benign according to our data. Variant chr17-50185616-A-G is described in ClinVar as [Benign]. Clinvar id is 456789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50185616-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.087 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00403 (613/152128) while in subpopulation AFR AF= 0.014 (581/41482). AF 95% confidence interval is 0.0131. There are 4 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
High AC in GnomAd4 at 613 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL1A1NM_000088.4 linkuse as main transcriptc.4281T>C p.Ile1427= synonymous_variant 51/51 ENST00000225964.10 NP_000079.2
COL1A1XM_011524341.2 linkuse as main transcriptc.4083T>C p.Ile1361= synonymous_variant 48/48 XP_011522643.1
COL1A1XM_005257058.5 linkuse as main transcriptc.4011T>C p.Ile1337= synonymous_variant 49/49 XP_005257115.2
COL1A1XM_005257059.5 linkuse as main transcriptc.3363T>C p.Ile1121= synonymous_variant 38/38 XP_005257116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL1A1ENST00000225964.10 linkuse as main transcriptc.4281T>C p.Ile1427= synonymous_variant 51/511 NM_000088.4 ENSP00000225964 P1

Frequencies

GnomAD3 genomes
AF:
0.00403
AC:
613
AN:
152010
Hom.:
4
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0140
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00103
AC:
258
AN:
249352
Hom.:
1
AF XY:
0.000822
AC XY:
111
AN XY:
134972
show subpopulations
Gnomad AFR exome
AF:
0.0141
Gnomad AMR exome
AF:
0.000636
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000358
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000367
AC:
536
AN:
1461812
Hom.:
5
Cov.:
32
AF XY:
0.000325
AC XY:
236
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0114
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000531
Gnomad4 OTH exome
AF:
0.000960
GnomAD4 genome
AF:
0.00403
AC:
613
AN:
152128
Hom.:
4
Cov.:
29
AF XY:
0.00382
AC XY:
284
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0140
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00173
Hom.:
0
Bravo
AF:
0.00456
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJun 25, 2018- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesSep 16, 2022- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
not specified Benign:2
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 17, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 19, 2019This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Osteogenesis imperfecta type I Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
7.5
DANN
Benign
0.67

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: rs41316725; hg19: chr17-48262977; API