Variant chr2-189003684-C-T 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.2608-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,573,600 control chromosomes in the GnomAD database, including 5,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.12 ( 2459 hom., cov: 32)

Exomes 𝑓: 0.040 ( 2790 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.57

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-189003684-C-T is Benign according to our data. Variant chr2-189003684-C-T is described in ClinVar as [Benign]. Clinvar id is 254964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 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.2608-50C>T		intron_variant		ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9 linkuse as main transcript	c.2608-50C>T	intron_variant	1	NM_000090.4	ENSP00000304408	P1	P02461-1
COL3A1	ENST00000450867.2 linkuse as main transcript	c.2509-50C>T	intron_variant	1		ENSP00000415346
COL3A1	ENST00000467886.1 linkuse as main transcript	n.43-50C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18115

AN:

151954

Hom.:

2438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0569

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.0908

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0321

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0587

AC:

14734

AN:

250928

Hom.:

1147

AF XY:

0.0534

AC XY:

7247

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.0346

Gnomad ASJ exome

AF:

0.0247

Gnomad EAS exome

AF:

0.0950

Gnomad SAS exome

AF:

0.0457

Gnomad FIN exome

AF:

0.0244

Gnomad NFE exome

AF:

0.0334

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0395

AC:

56201

AN:

1421528

Hom.:

2790

Cov.:

AF XY:

0.0387

AC XY:

27498

AN XY:

709814

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.0370

Gnomad4 ASJ exome

AF:

0.0241

Gnomad4 EAS exome

AF:

0.0838

Gnomad4 SAS exome

AF:

0.0435

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.0287

Gnomad4 OTH exome

AF:

0.0552

GnomAD4 genome

AF:

0.120

AC:

18185

AN:

152072

Hom.:

2459

Cov.:

AF XY:

0.117

AC XY:

8696

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.0567

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.0906

Gnomad4 SAS

AF:

0.0459

Gnomad4 FIN

AF:

0.0214

Gnomad4 NFE

AF:

0.0321

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0781

Hom.:

275

Bravo

AF:

0.131

Asia WGS

AF:

0.0920

AC:

319

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 18, 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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.068

DANN

Benign

0.43

BranchPoint Hunter

0.0

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