rs2271682

Variant names:

• chr2-189001473-T-A
• rs2271682
• NM_000090.4:c.2337+23T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-189001473-T-A
• chr2-189001473-T-C
• chr2-189001473-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000090.4(COL3A1):​c.2337+23T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,613,732 control chromosomes in the GnomAD database, including 428,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39625 hom., cov: 31)
  • Exomes 𝑓: 0.73 (389188 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0850
• Publications: 13 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-189001473-T-A is Benign according to our data. Variant chr2-189001473-T-A is described in ClinVar as Benign. ClinVar VariationId is 254962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.2337+23T>A		intron_variant	Intron 33 of 50	ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.2337+23T>A		intron_variant	Intron 33 of 50	1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2	c.2238+23T>A		intron_variant	Intron 32 of 49	1		ENSP00000415346.2
COL3A1	ENST00000713745.1	c.2184+23T>A		intron_variant	Intron 31 of 48			ENSP00000519049.1
COL3A1	ENST00000713744.1	c.2337+23T>A		intron_variant	Intron 33 of 48			ENSP00000519048.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109272 AN: 151950 Hom.: 39587 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.696

GnomAD2 exomes AF: 0.764 AC: 192001 AN: 251374 AF XY: 0.763

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.842

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.931

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.705

Gnomad OTH exome AF: 0.724

GnomAD4 exome AF: 0.727 AC: 1063123 AN: 1461664 Hom.: 389188 Cov.: 47 AF XY: 0.730 AC XY: 530703 AN XY: 727138

African (AFR) AF: 0.661 AC: 22122 AN: 33476

American (AMR) AF: 0.832 AC: 37227 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 17087 AN: 26136

East Asian (EAS) AF: 0.914 AC: 36267 AN: 39700

South Asian (SAS) AF: 0.840 AC: 72476 AN: 86254

European-Finnish (FIN) AF: 0.818 AC: 43707 AN: 53416

Middle Eastern (MID) AF: 0.617 AC: 3557 AN: 5768

European-Non Finnish (NFE) AF: 0.708 AC: 786804 AN: 1111804

Other (OTH) AF: 0.727 AC: 43876 AN: 60386

GnomAD4 genome AF: 0.719 AC: 109364 AN: 152068 Hom.: 39625 Cov.: 31 AF XY: 0.727 AC XY: 53996 AN XY: 74320

African (AFR) AF: 0.668 AC: 27720 AN: 41470

American (AMR) AF: 0.745 AC: 11371 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2265 AN: 3466

East Asian (EAS) AF: 0.925 AC: 4794 AN: 5180

South Asian (SAS) AF: 0.842 AC: 4049 AN: 4810

European-Finnish (FIN) AF: 0.834 AC: 8827 AN: 10588

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48144 AN: 67974

Other (OTH) AF: 0.695 AC: 1466 AN: 2108

Alfa AF: 0.717 Hom.: 7151

Bravo AF: 0.710

Asia WGS AF: 0.839 AC: 2921 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Ehlers-Danlos syndrome, type 4 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	-0.89
CADD	Benign	6.3
DANN	Benign	0.33
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271682; hg19: chr2-189866199;