rs10194304

Variant names:

• chr2-189006901-C-T
• rs10194304
• NM_000090.4:c.3202-36C>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.3202-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,605,714 control chromosomes in the GnomAD database, including 2,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (1189 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1501 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.23
• Publications: 3 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)

ENSG00000295704 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-189006901-C-T is Benign according to our data. Variant chr2-189006901-C-T is described in ClinVar as Benign. ClinVar VariationId is 254967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 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.3202-36C>T		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.3202-36C>T		intron	N/A	ENSP00000304408.4
	COL3A1	ENST00000450867.2	TSL:1	c.3103-36C>T		intron	N/A	ENSP00000415346.2
	COL3A1	ENST00000879201.1		c.3193-36C>T		intron	N/A	ENSP00000549260.1

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12951 AN: 151590 Hom.: 1185 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0263

Gnomad EAS AF: 0.00700

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0677

GnomAD2 exomes AF: 0.0387 AC: 9722 AN: 251022 AF XY: 0.0346

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.0281

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.00756

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0379

GnomAD4 exome AF: 0.0305 AC: 44357 AN: 1454004 Hom.: 1501 Cov.: 30 AF XY: 0.0295 AC XY: 21346 AN XY: 723758

African (AFR) AF: 0.241 AC: 8029 AN: 33254

American (AMR) AF: 0.0296 AC: 1322 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 522 AN: 26066

East Asian (EAS) AF: 0.00624 AC: 247 AN: 39572

South Asian (SAS) AF: 0.0145 AC: 1247 AN: 86026

European-Finnish (FIN) AF: 0.0214 AC: 1141 AN: 53254

Middle Eastern (MID) AF: 0.0415 AC: 234 AN: 5640

European-Non Finnish (NFE) AF: 0.0265 AC: 29294 AN: 1105516

Other (OTH) AF: 0.0387 AC: 2321 AN: 60028

GnomAD4 genome AF: 0.0856 AC: 12983 AN: 151710 Hom.: 1189 Cov.: 31 AF XY: 0.0833 AC XY: 6172 AN XY: 74110

African (AFR) AF: 0.237 AC: 9805 AN: 41348

American (AMR) AF: 0.0438 AC: 669 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0263 AC: 91 AN: 3466

East Asian (EAS) AF: 0.00701 AC: 36 AN: 5132

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4816

European-Finnish (FIN) AF: 0.0185 AC: 194 AN: 10492

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0286 AC: 1943 AN: 67880

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0512 Hom.: 198

Bravo AF: 0.0934

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.62
PhyloP100		-1.2
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: rs10194304; hg19: chr2-189871627;