rs3106796

Variant names:

• chr2-188985047-A-G
• rs3106796
• NM_000090.4:c.282+85A>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.282+85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,435,190 control chromosomes in the GnomAD database, including 139,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11604 hom., cov: 31)
  • Exomes 𝑓: 0.44 (128318 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.467
• Publications: 12 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)

ENSG00000304419 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-188985047-A-G is Benign according to our data. Variant chr2-188985047-A-G is described in ClinVar as Benign. ClinVar VariationId is 673782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.282+85A>G		intron_variant	Intron 2 of 50	ENST00000304636.9	NP_000081.2
LOC105373791	XR_007087614.1	n.-228T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.282+85A>G		intron_variant	Intron 2 of 50	1	NM_000090.4	ENSP00000304408.4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54020 AN: 151682 Hom.: 11604 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.440 AC: 564256 AN: 1283388 Hom.: 128318 Cov.: 18 AF XY: 0.438 AC XY: 282697 AN XY: 645422

African (AFR) AF: 0.0944 AC: 2753 AN: 29158

American (AMR) AF: 0.545 AC: 22697 AN: 41656

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 7852 AN: 24804

East Asian (EAS) AF: 0.581 AC: 21828 AN: 37578

South Asian (SAS) AF: 0.445 AC: 35910 AN: 80658

European-Finnish (FIN) AF: 0.546 AC: 28535 AN: 52232

Middle Eastern (MID) AF: 0.215 AC: 1166 AN: 5418

European-Non Finnish (NFE) AF: 0.440 AC: 421113 AN: 957752

Other (OTH) AF: 0.414 AC: 22402 AN: 54132

GnomAD4 genome AF: 0.356 AC: 54028 AN: 151802 Hom.: 11604 Cov.: 31 AF XY: 0.365 AC XY: 27055 AN XY: 74192

African (AFR) AF: 0.112 AC: 4635 AN: 41496

American (AMR) AF: 0.448 AC: 6812 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1069 AN: 3462

East Asian (EAS) AF: 0.606 AC: 3116 AN: 5138

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4816

European-Finnish (FIN) AF: 0.560 AC: 5917 AN: 10566

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29137 AN: 67814

Other (OTH) AF: 0.326 AC: 686 AN: 2104

Alfa AF: 0.408 Hom.: 31328

Bravo AF: 0.338

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 16, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.47
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: rs3106796; hg19: chr2-189849773; COSMIC: COSV58584432;