NM_000090.4:c.2284-450G>A

Variant names:

• chr2-189000947-G-A
• rs1040187
• NM_000090.4:c.2284-450G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000090.4(COL3A1):​c.2284-450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,074 control chromosomes in the GnomAD database, including 39,619 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39619 hom., cov: 32)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.2284-450G>A		intron_variant	Intron 32 of 50	ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.2284-450G>A		intron_variant	Intron 32 of 50	1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2	c.2185-450G>A		intron_variant	Intron 31 of 49	1		ENSP00000415346.2
COL3A1	ENST00000713745.1	c.2131-450G>A		intron_variant	Intron 30 of 48			ENSP00000519049.1
COL3A1	ENST00000713744.1	c.2284-450G>A		intron_variant	Intron 32 of 48			ENSP00000519048.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109265 AN: 151956 Hom.: 39583 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.694

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.719 AC: 109355 AN: 152074 Hom.: 39619 Cov.: 32 AF XY: 0.727 AC XY: 54003 AN XY: 74318

African (AFR) AF: 0.668 AC: 27725 AN: 41496

American (AMR) AF: 0.745 AC: 11368 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2264 AN: 3470

East Asian (EAS) AF: 0.925 AC: 4789 AN: 5176

South Asian (SAS) AF: 0.842 AC: 4055 AN: 4818

European-Finnish (FIN) AF: 0.834 AC: 8827 AN: 10580

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.708 AC: 48136 AN: 67956

Other (OTH) AF: 0.693 AC: 1466 AN: 2114

Alfa AF: 0.716 Hom.: 8090

Bravo AF: 0.710

Asia WGS AF: 0.840 AC: 2911 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.80
DANN	Benign	0.53
PhyloP100		-0.14
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: rs1040187; hg19: chr2-189865673;