rs3215251

chr2-189001616-AC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000090.4(COL3A1):c.2391+28del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,613,292 control chromosomes in the GnomAD database, including 5,399 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2610 hom., cov: 30)
  • Exomes 𝑓: 0.033 (2789 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96

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 -16 ACMG points.

• BP6: Variant 2-189001616-AC-A is Benign according to our data. Variant chr2-189001616-AC-A is described in ClinVar as [Benign]. Clinvar id is 254963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4	c.2391+28del		intron_variant		ENST00000304636.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9	c.2391+28del		intron_variant		1	NM_000090.4	P1
COL3A1	ENST00000450867.2	c.2292+28del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17995 AN: 151972 Hom.: 2589 Cov.: 30

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0545 AC: 13699 AN: 251350 Hom.: 1202 AF XY: 0.0488 AC XY: 6636 AN XY: 135864

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.0322

Gnomad ASJ exome AF: 0.0242

Gnomad EAS exome AF: 0.0933

Gnomad SAS exome AF: 0.0470

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.0239

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0327 AC: 47798 AN: 1461202 Hom.: 2789 Cov.: 33 AF XY: 0.0322 AC XY: 23381 AN XY: 726904

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.0355

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.0827

Gnomad4 SAS exome AF: 0.0447

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.0516

GnomAD4 genome AF: 0.119 AC: 18061 AN: 152090 Hom.: 2610 Cov.: 30 AF XY: 0.115 AC XY: 8579 AN XY: 74388

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0229

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0169 Hom.: 42

Bravo AF: 0.132

Asia WGS AF: 0.0930 AC: 325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 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

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: rs3215251; hg19: chr2-189866342;