Variant chr2-188997236-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000090.4(COL3A1):c.1815+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,613,690 control chromosomes in the GnomAD database, including 2,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 1307 hom., cov: 30)

Exomes 𝑓: 0.013 ( 1274 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.632

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-188997236-A-G is Benign according to our data. Variant chr2-188997236-A-G is described in ClinVar as [Benign]. Clinvar id is 136846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-188997236-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL3A1	NM_000090.4 linkuse as main transcript	c.1815+18A>G		intron_variant		ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9 linkuse as main transcript	c.1815+18A>G		intron_variant		1	NM_000090.4	ENSP00000304408	P1	P02461-1
COL3A1	ENST00000450867.2 linkuse as main transcript	c.1716+18A>G		intron_variant		1		ENSP00000415346

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11560

AN:

151760

Hom.:

1304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.0679

GnomAD3 exomes

AF:

0.0311

AC:

7814

AN:

251390

Hom.:

615

AF XY:

0.0273

AC XY:

3705

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.0863

Gnomad SAS exome

AF:

0.0328

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0132

AC:

19299

AN:

1461812

Hom.:

1274

Cov.:

AF XY:

0.0129

AC XY:

9410

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.0188

Gnomad4 ASJ exome

AF:

0.00275

Gnomad4 EAS exome

AF:

0.0766

Gnomad4 SAS exome

AF:

0.0313

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.00216

Gnomad4 OTH exome

AF:

0.0271

GnomAD4 genome

AF:

0.0763

AC:

11590

AN:

151878

Hom.:

1307

Cov.:

AF XY:

0.0748

AC XY:

5554

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.0814

Gnomad4 SAS

AF:

0.0323

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.0672

Alfa

AF:

0.0372

Hom.:

122

Bravo

AF:

0.0869

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 13, 2012	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 28, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ehlers-Danlos syndrome, type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.12

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over