dbSNP rs2271679: COL3A1:c.1293+15T>A (chr2-188994347-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000090.4(COL3A1):c.1293+15T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,613,044 control chromosomes in the GnomAD database, including 6,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2992 hom., cov: 32)

Exomes 𝑓: 0.033 ( 3172 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.26

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-188994347-T-A is Benign according to our data. Variant chr2-188994347-T-A is described in ClinVar as [Benign]. Clinvar id is 35961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-188994347-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4 link	c.1293+15T>A		intron_variant	Intron 18 of 50	ENST00000304636.9	NP_000081.2	P02461-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9 link	c.1293+15T>A		intron_variant	Intron 18 of 50	1	NM_000090.4	ENSP00000304408.4		P02461-1
COL3A1	ENST00000450867.2 link	c.1194+15T>A		intron_variant	Intron 17 of 49	1		ENSP00000415346.2		H7C435

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19163

AN:

152030

Hom.:

2971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.0883

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.0134

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.0565

AC:

14176

AN:

250700

Hom.:

1372

AF XY:

0.0503

AC XY:

6810

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.0331

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.0927

Gnomad SAS exome

AF:

0.0477

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.0240

Gnomad OTH exome

AF:

0.0478

GnomAD4 exome

AF:

0.0335

AC:

48920

AN:

1460896

Hom.:

3172

Cov.:

AF XY:

0.0329

AC XY:

23885

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.0368

Gnomad4 ASJ exome

AF:

0.0235

Gnomad4 EAS exome

AF:

0.0823

Gnomad4 SAS exome

AF:

0.0455

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.0200

Gnomad4 OTH exome

AF:

0.0531

GnomAD4 genome

AF:

0.126

AC:

19229

AN:

152148

Hom.:

2992

Cov.:

AF XY:

0.122

AC XY:

9101

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.0591

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.0881

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.0134

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.0340

Hom.:

Bravo

AF:

0.142

Asia WGS

AF:

0.0940

AC:

327

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Nov 05, 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. -

Apr 04, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1293+15T>A in intron 18 of COL3A1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 37.0% (1631/4404) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs2271679). -

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

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, type 4

Benign:2

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 aortopathy

Benign:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.27

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over