rs1057297

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000088.4(COL1A1):c.177G>T(p.Arg59Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,614,152 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 238 hom., cov: 33)

Exomes 𝑓: 0.015 ( 412 hom. )

Consequence

COL1A1
NM_000088.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.928

Publications

10 publications found

Variant links:

COSMIC-nc: COSV56806402

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]

COL1A1 links:

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

TILAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 17-50199874-C-A is Benign according to our data. Variant chr17-50199874-C-A is described in ClinVar as Benign. ClinVar VariationId is 254945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.928 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A1	NM_000088.4 link	c.177G>T	p.Arg59Arg	synonymous_variant	Exon 2 of 51	ENST00000225964.10	NP_000079.2	P02452
COL1A1	XM_011524341.2 link	c.177G>T	p.Arg59Arg	synonymous_variant	Exon 2 of 48		XP_011522643.1
COL1A1	XM_005257058.5 link	c.177G>T	p.Arg59Arg	synonymous_variant	Exon 2 of 49		XP_005257115.2
COL1A1	XM_005257059.5 link	c.177G>T	p.Arg59Arg	synonymous_variant	Exon 2 of 38		XP_005257116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL1A1	ENST00000225964.10 link	c.177G>T	p.Arg59Arg	synonymous_variant	Exon 2 of 51	1	NM_000088.4	ENSP00000225964.6	P02452
COL1A1	ENST00000507689.1 link	c.231G>T	p.Arg77Arg	synonymous_variant	Exon 1 of 4	2		ENSP00000460459.1	I3L3H7
COL1A1	ENST00000474644.1 link	n.296G>T		non_coding_transcript_exon_variant	Exon 2 of 4	3
TILAM	ENST00000509943.2 link	n.-2C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5830

AN:

152160

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0384

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.0206

AC:

5168

AN:

251368

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0148

AC:

21605

AN:

1461874

Hom.:

412

Cov.:

AF XY:

0.0154

AC XY:

11198

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.106

AC:

3544

AN:

33480

American (AMR)

AF:

0.0106

AC:

475

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0166

AC:

435

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0391

AC:

3372

AN:

86256

European-Finnish (FIN)

AF:

0.0114

AC:

610

AN:

53414

Middle Eastern (MID)

AF:

0.0198

AC:

114

AN:

5764

European-Non Finnish (NFE)

AF:

0.0107

AC:

11863

AN:

1112008

Other (OTH)

AF:

0.0196

AC:

1186

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1439

2879

4318

5758

7197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0384

AC:

5841

AN:

152278

Hom.:

238

Cov.:

AF XY:

0.0374

AC XY:

2785

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.107

AC:

4430

AN:

41548

American (AMR)

AF:

0.0151

AC:

231

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0384

AC:

185

AN:

4814

European-Finnish (FIN)

AF:

0.0106

AC:

113

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

743

AN:

68018

Other (OTH)

AF:

0.0284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

269

539

808

1078

1347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0208

Hom.:

173

Bravo

AF:

0.0405

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0111

EpiControl

AF:

0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Osteogenesis imperfecta

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 16, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Sep 08, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Ehlers-Danlos syndrome

Benign:1

Jul 07, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, arthrochalasia type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Infantile cortical hyperostosis

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cardiovascular phenotype

Benign:1

Dec 17, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.93

PromoterAI

-0.069

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over