rs200449080

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000090.4(COL3A1):c.3256-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 1,550,406 control chromosomes in the GnomAD database, including 57 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 0.0057 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0074 ( 54 hom. )

Consequence

COL3A1
NM_000090.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235

Publications

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

COL3A1 links:

ENSG00000295704 (HGNC:):

ENSG00000295704 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-189007472-G-A is Benign according to our data. Variant chr2-189007472-G-A is described in ClinVar as Benign. ClinVar VariationId is 254969.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00575 (874/152094) while in subpopulation NFE AF = 0.00921 (626/67994). AF 95% confidence interval is 0.00861. There are 3 homozygotes in GnomAd4. There are 441 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000090.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	NM_000090.4	MANE Select	c.3256-28G>A		intron	N/A	NP_000081.2	P02461-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL3A1	ENST00000304636.9	TSL:1 MANE Select	c.3256-28G>A	intron	N/A	ENSP00000304408.4	P02461-1
COL3A1	ENST00000450867.2	TSL:1	c.3157-28G>A	intron	N/A	ENSP00000415346.2	H7C435
COL3A1	ENST00000879201.1		c.3247-28G>A	intron	N/A	ENSP00000549260.1

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

874

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00794

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00921

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00541

AC:

1216

AN:

224822

AF XY:

0.00537

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.000524

Gnomad EAS exome

AF:

0.00202

Gnomad FIN exome

AF:

0.00692

Gnomad NFE exome

AF:

0.00896

Gnomad OTH exome

AF:

0.00536

GnomAD4 exome

AF:

0.00736

AC:

10290

AN:

1398312

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

4985

AN XY:

697042

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

31952

American (AMR)

AF:

0.00231

AC:

AN:

42798

Ashkenazi Jewish (ASJ)

AF:

0.000785

AC:

AN:

25468

East Asian (EAS)

AF:

0.00107

AC:

AN:

38472

South Asian (SAS)

AF:

0.00125

AC:

103

AN:

82642

European-Finnish (FIN)

AF:

0.00823

AC:

431

AN:

52356

Middle Eastern (MID)

AF:

0.00141

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00872

AC:

9246

AN:

1060780

Other (OTH)

AF:

0.00514

AC:

299

AN:

58190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

504

1007

1511

2014

2518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00575

AC:

874

AN:

152094

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

441

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41506

American (AMR)

AF:

0.00426

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.00208

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00794

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00921

AC:

626

AN:

67994

Other (OTH)

AF:

0.00142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00884

Hom.:

Bravo

AF:

0.00471

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.23

BranchPoint Hunter

0.0

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over