Genetic Variant COL3A1:c.80-1018T>C (chr2-188983742-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000090.4(COL3A1):c.80-1018T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,846 control chromosomes in the GnomAD database, including 11,442 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 11442 hom., cov: 32)

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.202

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant Ehlers-Danlos syndrome, vascular type
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
Ehlers-Danlos syndrome, vascular type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
polymicrogyria with or without vascular-type Ehlers-Danlos syndrome
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

COL3A1 links:

ENSG00000304419 (HGNC:):

ENSG00000304419 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4 link	c.80-1018T>C		intron_variant	Intron 1 of 50	ENST00000304636.9	NP_000081.2	P02461-1
LOC105373791	XR_007087614.1 link	n.109+969A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9 link	c.80-1018T>C		intron_variant	Intron 1 of 50	1	NM_000090.4	ENSP00000304408.4		P02461-1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53816

AN:

151728

Hom.:

11440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.354

AC:

53826

AN:

151846

Hom.:

11442

Cov.:

AF XY:

0.364

AC XY:

26980

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.114

AC:

4734

AN:

41508

American (AMR)

AF:

0.446

AC:

6782

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1082

AN:

3460

East Asian (EAS)

AF:

0.602

AC:

3099

AN:

5150

South Asian (SAS)

AF:

0.464

AC:

2236

AN:

4820

European-Finnish (FIN)

AF:

0.556

AC:

5875

AN:

10566

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28851

AN:

67836

Other (OTH)

AF:

0.328

AC:

693

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1623

3245

4868

6490

8113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.411

Hom.:

6687

Bravo

AF:

0.337

Asia WGS

AF:

0.498

AC:

1731

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

(source)

DANN

Benign

0.53

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over