rs10194475

Variant names:

• chr2-189006897-G-A
• rs10194475
• NM_000090.4:c.3202-40G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-189006897-G-A
• chr2-189006897-G-C

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.3202-40G>A 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 1,604,162 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (1191 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1498 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.25
• Publications: 4 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=-0.88).
• BP6: Variant 2-189006897-G-A is Benign according to our data. Variant chr2-189006897-G-A is described in ClinVar as Benign. ClinVar VariationId is 254968.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.3202-40G>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.3202-40G>A		intron	N/A	ENSP00000304408.4
	COL3A1	ENST00000450867.2	TSL:1	c.3103-40G>A		intron	N/A	ENSP00000415346.2
	COL3A1	ENST00000713745.1		c.3049-40G>A		intron	N/A	ENSP00000519049.1

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12952 AN: 151714 Hom.: 1187 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00698

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0680

GnomAD2 exomes AF: 0.0386 AC: 9699 AN: 250988 AF XY: 0.0346

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.0282

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.00724

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0380

GnomAD4 exome AF: 0.0305 AC: 44307 AN: 1452330 Hom.: 1498 Cov.: 29 AF XY: 0.0295 AC XY: 21310 AN XY: 723022

African (AFR) AF: 0.241 AC: 8019 AN: 33212

American (AMR) AF: 0.0296 AC: 1322 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 522 AN: 26040

East Asian (EAS) AF: 0.00607 AC: 240 AN: 39544

South Asian (SAS) AF: 0.0145 AC: 1245 AN: 85986

European-Finnish (FIN) AF: 0.0214 AC: 1140 AN: 53240

Middle Eastern (MID) AF: 0.0418 AC: 235 AN: 5626

European-Non Finnish (NFE) AF: 0.0265 AC: 29261 AN: 1103996

Other (OTH) AF: 0.0387 AC: 2323 AN: 60022

GnomAD4 genome AF: 0.0855 AC: 12983 AN: 151832 Hom.: 1191 Cov.: 31 AF XY: 0.0832 AC XY: 6173 AN XY: 74194

African (AFR) AF: 0.237 AC: 9804 AN: 41358

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

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.00699 AC: 36 AN: 5148

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4812

European-Finnish (FIN) AF: 0.0185 AC: 195 AN: 10530

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1942 AN: 67930

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0531 Hom.: 136

Bravo AF: 0.0934

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		-1.3
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: rs10194475; hg19: chr2-189871623;