rs7579903

Variant names:

• chr2-188997371-G-A
• rs7579903
• NM_000090.4:c.1851G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000090.4(COL3A1):​c.1851G>A​(p.Gln617Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,608,662 control chromosomes in the GnomAD database, including 17,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1961 hom., cov: 30)
  • Exomes 𝑓: 0.14 (15382 hom.)
• Consequence: COL3A1 NM_000090.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:17
• Conservation: PhyloP100: -0.278
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-188997371-G-A is Benign according to our data. Variant chr2-188997371-G-A is described in ClinVar as Benign. ClinVar VariationId is 136848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.278 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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.1851G>A	p.Gln617Gln	synonymous	Exon 26 of 51	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.1851G>A	p.Gln617Gln	synonymous	Exon 26 of 51	ENSP00000304408.4	P02461-1
	COL3A1	ENST00000450867.2	TSL:1	c.1752G>A	p.Gln584Gln	synonymous	Exon 25 of 50	ENSP00000415346.2	H7C435
	COL3A1	ENST00000879201.1		c.1842G>A	p.Gln614Gln	synonymous	Exon 26 of 51	ENSP00000549260.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23621 AN: 151906 Hom.: 1960 Cov.: 30

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.123 AC: 30763 AN: 251060 AF XY: 0.124

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.0783

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.00125

Gnomad FIN exome AF: 0.0948

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.139 AC: 202690 AN: 1456638 Hom.: 15382 Cov.: 34 AF XY: 0.138 AC XY: 100368 AN XY: 724838

African (AFR) AF: 0.224 AC: 7474 AN: 33352

American (AMR) AF: 0.0823 AC: 3679 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3707 AN: 26106

East Asian (EAS) AF: 0.000957 AC: 38 AN: 39698

South Asian (SAS) AF: 0.106 AC: 9152 AN: 86168

European-Finnish (FIN) AF: 0.0983 AC: 5250 AN: 53408

Middle Eastern (MID) AF: 0.196 AC: 1127 AN: 5750

European-Non Finnish (NFE) AF: 0.148 AC: 163743 AN: 1107178

Other (OTH) AF: 0.141 AC: 8520 AN: 60272

GnomAD4 genome AF: 0.155 AC: 23638 AN: 152024 Hom.: 1961 Cov.: 30 AF XY: 0.153 AC XY: 11333 AN XY: 74310

African (AFR) AF: 0.217 AC: 8991 AN: 41408

American (AMR) AF: 0.132 AC: 2016 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5172

South Asian (SAS) AF: 0.103 AC: 497 AN: 4808

European-Finnish (FIN) AF: 0.0896 AC: 949 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.149 AC: 10114 AN: 67974

Other (OTH) AF: 0.158 AC: 335 AN: 2114

Alfa AF: 0.152 Hom.: 3973

Bravo AF: 0.160

Asia WGS AF: 0.0980 AC: 340 AN: 3478

EpiCase AF: 0.149

EpiControl AF: 0.152

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	5	Ehlers-Danlos syndrome, type 4 (5)
-	-	2	Familial thoracic aortic aneurysm and aortic dissection (2)
-	-	2	not provided (2)
-	-	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	-0.74
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		-0.28
Mutation Taster		=99/1	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: rs7579903; hg19: chr2-189862097; COSMIC: COSV108098103; COSMIC: COSV108098103;