rs3106796

Positions:

• chr2-188985047-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000090.4(COL3A1):​c.282+85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,435,190 control chromosomes in the GnomAD database, including 139,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11604 hom., cov: 31)
  • Exomes 𝑓: 0.44 (128318 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.467

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-188985047-A-G is Benign according to our data. Variant chr2-188985047-A-G is described in ClinVar as [Benign]. Clinvar id is 673782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.282+85A>G		intron_variant		ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.282+85A>G		intron_variant		1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2	c.282+85A>G		intron_variant		1		ENSP00000415346.2
COL3A1	ENST00000470167.1	n.463A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54020 AN: 151682 Hom.: 11604 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.440 AC: 564256 AN: 1283388 Hom.: 128318 Cov.: 18 AF XY: 0.438 AC XY: 282697 AN XY: 645422

Gnomad4 AFR exome AF: 0.0944

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.581

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.546

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.356 AC: 54028 AN: 151802 Hom.: 11604 Cov.: 31 AF XY: 0.365 AC XY: 27055 AN XY: 74192

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.326

Alfa AF: 0.413 Hom.: 20782

Bravo AF: 0.338

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs3106796; hg19: chr2-189849773; COSMIC: COSV58584432;