rs3811161

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000093.5(COL5A1):c.2845-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 987,228 control chromosomes in the GnomAD database, including 132,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20867 hom., cov: 32)

Exomes 𝑓: 0.51 ( 111401 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.78

Publications

5 publications found

Variant links:

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, classic type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
Ehlers-Danlos syndrome, classic type, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
arterial disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COL5A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 9-134796731-A-G is Benign according to our data. Variant chr9-134796731-A-G is described in ClinVar as Benign. ClinVar VariationId is 672276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.2845-117A>G	intron_variant	Intron 35 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.2845-117A>G	intron_variant	Intron 35 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.2845-117A>G	intron_variant	Intron 35 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.2845-117A>G		intron_variant	Intron 35 of 65	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.2845-117A>G		intron_variant	Intron 35 of 65	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79047

AN:

151924

Hom.:

20852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.511

GnomAD4 exome

AF:

0.512

AC:

427645

AN:

835186

Hom.:

111401

AF XY:

0.513

AC XY:

225492

AN XY:

439414

show subpopulations

African (AFR)

AF:

0.573

AC:

12330

AN:

21530

American (AMR)

AF:

0.466

AC:

19372

AN:

41562

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

11738

AN:

21888

East Asian (EAS)

AF:

0.762

AC:

27968

AN:

36720

South Asian (SAS)

AF:

0.545

AC:

39597

AN:

72654

European-Finnish (FIN)

AF:

0.456

AC:

23415

AN:

51298

Middle Eastern (MID)

AF:

0.532

AC:

2239

AN:

4206

European-Non Finnish (NFE)

AF:

0.495

AC:

270262

AN:

545594

Other (OTH)

AF:

0.522

AC:

20724

AN:

39734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12172

24345

36517

48690

60862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5012

10024

15036

20048

25060

<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:

0.520

AC:

79113

AN:

152042

Hom.:

20867

Cov.:

AF XY:

0.518

AC XY:

38531

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.571

AC:

23688

AN:

41462

American (AMR)

AF:

0.450

AC:

6874

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

1870

AN:

3470

East Asian (EAS)

AF:

0.773

AC:

3982

AN:

5154

South Asian (SAS)

AF:

0.551

AC:

2655

AN:

4820

European-Finnish (FIN)

AF:

0.458

AC:

4848

AN:

10590

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33696

AN:

67948

Other (OTH)

AF:

0.511

AC:

1078

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1955

3909

5864

7818

9773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.517

Hom.:

2675

Bravo

AF:

0.523

Asia WGS

AF:

0.653

AC:

2268

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.15

(source)

DANN

Benign

0.20

PhyloP100

-2.8

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over