rs10204508

Variant names:

• chr2-189010147-C-A
• rs10204508
• NM_000090.4:c.3824-31C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-189010147-C-A
• chr2-189010147-C-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.3824-31C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,608,478 control chromosomes in the GnomAD database, including 38,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4438 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33810 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.131
• Publications: 8 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=-0.82).
• BP6: Variant 2-189010147-C-A is Benign according to our data. Variant chr2-189010147-C-A is described in ClinVar as Benign. ClinVar VariationId is 254970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	NM_000090.4	MANE Select	c.3824-31C>A		intron	N/A	NP_000081.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	ENST00000304636.9	TSL:1 MANE Select	c.3824-31C>A		intron	N/A	ENSP00000304408.4
	COL3A1	ENST00000450867.2	TSL:1	c.3725-31C>A		intron	N/A	ENSP00000415346.2
	COL3A1	ENST00000713745.1		c.3671-31C>A		intron	N/A	ENSP00000519049.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35413 AN: 151998 Hom.: 4430 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0752

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.251

GnomAD2 exomes AF: 0.197 AC: 49299 AN: 250534 AF XY: 0.202

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.0672

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.211 AC: 307432 AN: 1456362 Hom.: 33810 Cov.: 30 AF XY: 0.212 AC XY: 153960 AN XY: 724820

African (AFR) AF: 0.317 AC: 10587 AN: 33348

American (AMR) AF: 0.123 AC: 5512 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7946 AN: 26094

East Asian (EAS) AF: 0.0852 AC: 3376 AN: 39636

South Asian (SAS) AF: 0.217 AC: 18721 AN: 86120

European-Finnish (FIN) AF: 0.153 AC: 8167 AN: 53366

Middle Eastern (MID) AF: 0.364 AC: 2095 AN: 5760

European-Non Finnish (NFE) AF: 0.215 AC: 237693 AN: 1107116

Other (OTH) AF: 0.221 AC: 13335 AN: 60212

GnomAD4 genome AF: 0.233 AC: 35436 AN: 152116 Hom.: 4438 Cov.: 33 AF XY: 0.230 AC XY: 17072 AN XY: 74374

African (AFR) AF: 0.309 AC: 12805 AN: 41456

American (AMR) AF: 0.186 AC: 2839 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1022 AN: 3472

East Asian (EAS) AF: 0.0750 AC: 388 AN: 5172

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1569 AN: 10602

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14849 AN: 67984

Other (OTH) AF: 0.256 AC: 540 AN: 2112

Alfa AF: 0.230 Hom.: 5112

Bravo AF: 0.239

Asia WGS AF: 0.174 AC: 604 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ehlers-Danlos syndrome, type 4 (1)
-	-	1	not specified (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	-0.82
CADD	Benign	6.4
DANN	Benign	0.60
PhyloP100		0.13
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: rs10204508; hg19: chr2-189874873; COSMIC: COSV58584394;