rs2271682

chr2-189001473-T-Achr2-189001473-T-Cchr2-189001473-T-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.2337+23T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,613,732 control chromosomes in the GnomAD database, including 428,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39625 hom., cov: 31)
  • Exomes 𝑓: 0.73 (389188 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0850

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=-0.89).
• BP6: Variant 2-189001473-T-A is Benign according to our data. Variant chr2-189001473-T-A is described in ClinVar as [Benign]. Clinvar id is 254962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4	c.2337+23T>A		intron_variant		ENST00000304636.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9	c.2337+23T>A		intron_variant		1	NM_000090.4	P1
COL3A1	ENST00000450867.2	c.2238+23T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109272 AN: 151950 Hom.: 39587 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.696

GnomAD3 exomes AF: 0.764 AC: 192001 AN: 251374 Hom.: 74262 AF XY: 0.763 AC XY: 103650 AN XY: 135864

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.842

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.931

Gnomad SAS exome AF: 0.843

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.705

Gnomad OTH exome AF: 0.724

GnomAD4 exome AF: 0.727 AC: 1063123 AN: 1461664 Hom.: 389188 Cov.: 47 AF XY: 0.730 AC XY: 530703 AN XY: 727138

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.654

Gnomad4 EAS exome AF: 0.914

Gnomad4 SAS exome AF: 0.840

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.727

GnomAD4 genome AF: 0.719 AC: 109364 AN: 152068 Hom.: 39625 Cov.: 31 AF XY: 0.727 AC XY: 53996 AN XY: 74320

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.695

Alfa AF: 0.717 Hom.: 7151

Bravo AF: 0.710

Asia WGS AF: 0.839 AC: 2921 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

-

- -

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. -

Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Ehlers-Danlos syndrome, type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.3
Dann	Benign	0.33

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: rs2271682; hg19: chr2-189866199;