rs13306272

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000090.4(COL3A1):c.1978-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,608,644 control chromosomes in the GnomAD database, including 53,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4504 hom., cov: 32)

Exomes 𝑓: 0.26 ( 48561 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Splicing: ADA: 0.00002065

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.782

Publications

12 publications found

Variant links:

Genes affected

COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]

COL3A1 Gene-Disease associations (from GenCC):

autosomal dominant Ehlers-Danlos syndrome, vascular type
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
Ehlers-Danlos syndrome, vascular type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
polymicrogyria with or without vascular-type Ehlers-Danlos syndrome
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

COL3A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-188998663-C-T is Benign according to our data. Variant chr2-188998663-C-T is described in ClinVar as Benign. ClinVar VariationId is 136851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4 link	c.1978-11C>T		intron_variant	Intron 28 of 50	ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL3A1	ENST00000304636.9 link	c.1978-11C>T	intron_variant	Intron 28 of 50	1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2 link	c.1879-11C>T	intron_variant	Intron 27 of 49	1		ENSP00000415346.2
COL3A1	ENST00000713745.1 link	c.1825-11C>T	intron_variant	Intron 26 of 48			ENSP00000519049.1
COL3A1	ENST00000713744.1 link	c.1978-11C>T	intron_variant	Intron 28 of 48			ENSP00000519048.1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36454

AN:

151882

Hom.:

4498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.263

AC:

66004

AN:

250800

AF XY:

0.272

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.255

AC:

372154

AN:

1456646

Hom.:

48561

Cov.:

AF XY:

0.260

AC XY:

188332

AN XY:

724896

show subpopulations

African (AFR)

AF:

0.193

AC:

6455

AN:

33388

American (AMR)

AF:

0.249

AC:

11116

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

8180

AN:

26078

East Asian (EAS)

AF:

0.250

AC:

9886

AN:

39612

South Asian (SAS)

AF:

0.343

AC:

29569

AN:

86106

European-Finnish (FIN)

AF:

0.259

AC:

13801

AN:

53378

Middle Eastern (MID)

AF:

0.348

AC:

1999

AN:

5738

European-Non Finnish (NFE)

AF:

0.249

AC:

275563

AN:

1107434

Other (OTH)

AF:

0.259

AC:

15585

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

13655

27310

40965

54620

68275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9386

18772

28158

37544

46930

<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:

0.240

AC:

36469

AN:

151998

Hom.:

4504

Cov.:

AF XY:

0.242

AC XY:

17989

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.192

AC:

7945

AN:

41468

American (AMR)

AF:

0.240

AC:

3660

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1088

AN:

3468

East Asian (EAS)

AF:

0.231

AC:

1192

AN:

5170

South Asian (SAS)

AF:

0.336

AC:

1614

AN:

4810

European-Finnish (FIN)

AF:

0.262

AC:

2767

AN:

10554

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.257

AC:

17439

AN:

67954

Other (OTH)

AF:

0.261

AC:

549

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1430

2859

4289

5718

7148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.249

Hom.:

1791

Bravo

AF:

0.235

Asia WGS

AF:

0.249

AC:

865

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Apr 04, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1978-11C>T in intron 28 of COL3A1: This variant is not expected to have clinical significance because it has been identified in 26.1% (2242/8600) of European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs13306272). -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 13, 2012

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, type 4

Benign:4

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 23, 2022

Cohesion Phenomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Mar 15, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

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

-0.84

CADD

Benign

5.2

(source)

DANN

Benign

0.22

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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