2-188997236-A-G

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.1815+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,613,690 control chromosomes in the GnomAD database, including 2,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 1307 hom., cov: 30)

Exomes 𝑓: 0.013 ( 1274 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.632

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 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=-0.83).

BP6

Variant 2-188997236-A-G is Benign according to our data. Variant chr2-188997236-A-G is described in ClinVar as [Benign]. Clinvar id is 136846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-188997236-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4 link	c.1815+18A>G		intron_variant	Intron 25 of 50	ENST00000304636.9	NP_000081.2	P02461-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL3A1	ENST00000304636.9 link	c.1815+18A>G	intron_variant	Intron 25 of 50	1	NM_000090.4	ENSP00000304408.4	P02461-1
COL3A1	ENST00000450867.2 link	c.1716+18A>G	intron_variant	Intron 24 of 49	1		ENSP00000415346.2	H7C435
COL3A1	ENST00000713745.1 link	c.1662+18A>G	intron_variant	Intron 23 of 48			ENSP00000519049.1
COL3A1	ENST00000713744.1 link	c.1815+18A>G	intron_variant	Intron 25 of 48			ENSP00000519048.1

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11560

AN:

151760

Hom.:

1304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.0679

GnomAD2 exomes

AF:

0.0311

AC:

7814

AN:

251390

AF XY:

0.0273

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.0863

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0132

AC:

19299

AN:

1461812

Hom.:

1274

Cov.:

AF XY:

0.0129

AC XY:

9410

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.250

AC:

8354

AN:

33442

American (AMR)

AF:

0.0188

AC:

840

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00275

AC:

AN:

26136

East Asian (EAS)

AF:

0.0766

AC:

3040

AN:

39698

South Asian (SAS)

AF:

0.0313

AC:

2701

AN:

86256

European-Finnish (FIN)

AF:

0.00234

AC:

125

AN:

53414

Middle Eastern (MID)

AF:

0.0229

AC:

132

AN:

5768

European-Non Finnish (NFE)

AF:

0.00216

AC:

2401

AN:

1111978

Other (OTH)

AF:

0.0271

AC:

1634

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1047

2094

3140

4187

5234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0763

AC:

11590

AN:

151878

Hom.:

1307

Cov.:

AF XY:

0.0748

AC XY:

5554

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.245

AC:

10133

AN:

41304

American (AMR)

AF:

0.0310

AC:

474

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3466

East Asian (EAS)

AF:

0.0814

AC:

420

AN:

5160

South Asian (SAS)

AF:

0.0323

AC:

155

AN:

4800

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00319

AC:

217

AN:

67972

Other (OTH)

AF:

0.0672

AC:

142

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

439

879

1318

1758

2197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0507

Hom.:

436

Bravo

AF:

0.0869

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 05, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, type 4

Benign:1

Feb 04, 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

-0.83

CADD

Benign

0.12

(source)

DANN

Benign

0.54

PhyloP100

-0.63

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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2-188997236-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over