rs13306272

Variant names:

• chr2-188998663-C-T
• rs13306272
• NM_000090.4:c.1978-11C>T

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.1978-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,608,644 control chromosomes in the GnomAD database, including 53,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4504 hom., cov: 32)
  • Exomes 𝑓: 0.26 (48561 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Scores: Splicing: ADA: 0.00002065
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.782
• 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Ehlers-Danlos syndrome, vascular type

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• polymicrogyria with or without vascular-type Ehlers-Danlos syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-188998663-C-T is Benign according to our data. Variant chr2-188998663-C-T is described in ClinVar as Benign. ClinVar VariationId is 136851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000090.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	NM_000090.4	MANE Select	c.1978-11C>T		intron	N/A	NP_000081.2	P02461-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	ENST00000304636.9	TSL:1 MANE Select	c.1978-11C>T		intron	N/A	ENSP00000304408.4	P02461-1
	COL3A1	ENST00000450867.2	TSL:1	c.1879-11C>T		intron	N/A	ENSP00000415346.2	H7C435
	COL3A1	ENST00000879201.1		c.1969-11C>T		intron	N/A	ENSP00000549260.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36454 AN: 151882 Hom.: 4498 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.263 AC: 66004 AN: 250800 AF XY: 0.272

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.255 AC: 372154 AN: 1456646 Hom.: 48561 Cov.: 32 AF XY: 0.260 AC XY: 188332 AN XY: 724896

African (AFR) AF: 0.193 AC: 6455 AN: 33388

American (AMR) AF: 0.249 AC: 11116 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 8180 AN: 26078

East Asian (EAS) AF: 0.250 AC: 9886 AN: 39612

South Asian (SAS) AF: 0.343 AC: 29569 AN: 86106

European-Finnish (FIN) AF: 0.259 AC: 13801 AN: 53378

Middle Eastern (MID) AF: 0.348 AC: 1999 AN: 5738

European-Non Finnish (NFE) AF: 0.249 AC: 275563 AN: 1107434

Other (OTH) AF: 0.259 AC: 15585 AN: 60220

GnomAD4 genome AF: 0.240 AC: 36469 AN: 151998 Hom.: 4504 Cov.: 32 AF XY: 0.242 AC XY: 17989 AN XY: 74292

African (AFR) AF: 0.192 AC: 7945 AN: 41468

American (AMR) AF: 0.240 AC: 3660 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5170

South Asian (SAS) AF: 0.336 AC: 1614 AN: 4810

European-Finnish (FIN) AF: 0.262 AC: 2767 AN: 10554

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17439 AN: 67954

Other (OTH) AF: 0.261 AC: 549 AN: 2104

Alfa AF: 0.249 Hom.: 1791

Bravo AF: 0.235

Asia WGS AF: 0.249 AC: 865 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	4	Ehlers-Danlos syndrome, type 4 (4)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	not provided (1)
-	-	1	Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.22
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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: rs13306272; hg19: chr2-189863389;