rs7579903

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000090.4(COL3A1):c.1851G>A(p.Gln617Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,608,662 control chromosomes in the GnomAD database, including 17,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1961 hom., cov: 30)

Exomes 𝑓: 0.14 ( 15382 hom. )

Consequence

COL3A1
NM_000090.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -0.278

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-188997371-G-A is Benign according to our data. Variant chr2-188997371-G-A is described in ClinVar as Benign. ClinVar VariationId is 136848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.278 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4 link	c.1851G>A	p.Gln617Gln	synonymous_variant	Exon 26 of 51	ENST00000304636.9	NP_000081.2	P02461-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL3A1	ENST00000304636.9 link	c.1851G>A	p.Gln617Gln	synonymous_variant	Exon 26 of 51	1	NM_000090.4	ENSP00000304408.4	P02461-1
COL3A1	ENST00000450867.2 link	c.1752G>A	p.Gln584Gln	synonymous_variant	Exon 25 of 50	1		ENSP00000415346.2	H7C435
COL3A1	ENST00000713745.1 link	c.1698G>A	p.Gln566Gln	synonymous_variant	Exon 24 of 49			ENSP00000519049.1
COL3A1	ENST00000713744.1 link	c.1851G>A	p.Gln617Gln	synonymous_variant	Exon 26 of 49			ENSP00000519048.1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23621

AN:

151906

Hom.:

1960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.123

AC:

30763

AN:

251060

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0783

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.0948

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.139

AC:

202690

AN:

1456638

Hom.:

15382

Cov.:

AF XY:

0.138

AC XY:

100368

AN XY:

724838

show subpopulations

African (AFR)

AF:

0.224

AC:

7474

AN:

33352

American (AMR)

AF:

0.0823

AC:

3679

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3707

AN:

26106

East Asian (EAS)

AF:

0.000957

AC:

AN:

39698

South Asian (SAS)

AF:

0.106

AC:

9152

AN:

86168

European-Finnish (FIN)

AF:

0.0983

AC:

5250

AN:

53408

Middle Eastern (MID)

AF:

0.196

AC:

1127

AN:

5750

European-Non Finnish (NFE)

AF:

0.148

AC:

163743

AN:

1107178

Other (OTH)

AF:

0.141

AC:

8520

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

9027

18054

27080

36107

45134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5774

11548

17322

23096

28870

<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:

0.155

AC:

23638

AN:

152024

Hom.:

1961

Cov.:

AF XY:

0.153

AC XY:

11333

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.217

AC:

8991

AN:

41408

American (AMR)

AF:

0.132

AC:

2016

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

489

AN:

3470

East Asian (EAS)

AF:

0.00425

AC:

AN:

5172

South Asian (SAS)

AF:

0.103

AC:

497

AN:

4808

European-Finnish (FIN)

AF:

0.0896

AC:

949

AN:

10586

Middle Eastern (MID)

AF:

0.190

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.149

AC:

10114

AN:

67974

Other (OTH)

AF:

0.158

AC:

335

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

996

1992

2987

3983

4979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.152

Hom.:

3973

Bravo

AF:

0.160

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

EpiCase

AF:

0.149

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Nov 20, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Gln617Gln in exon 26 of COL3A1: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 15% (1263/8600) of European American chromosomes and 20% (877/4406) of African American chromoso mes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; db SNP rs7579903). -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 20, 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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Ehlers-Danlos syndrome, type 4

Benign:5

Sep 23, 2022

Cohesion Phenomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 03, 2024

All of Us Research Program, National Institutes of Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Mar 15, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

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. -

not provided

Benign:2

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

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

-0.74

CADD

Benign

4.8

(source)

DANN

Benign

0.63

PhyloP100

-0.28

Mutation Taster

=99/1

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