dbSNP rs2287802: COL5A3:c.850-131T>C (chr19-10002012-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015719.4(COL5A3):c.850-131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 639,208 control chromosomes in the GnomAD database, including 48,441 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 0.37 ( 10590 hom., cov: 30)

Exomes 𝑓: 0.39 ( 37851 hom. )

Consequence

COL5A3
NM_015719.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Publications

16 publications found

Variant links:

Genes affected

COL5A3 (HGNC:14864): (collagen type V alpha 3 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. Mutations in this gene are thought to be responsible for the symptoms of a subset of patients with Ehlers-Danlos syndrome type III. Messages of several sizes can be detected in northern blots but sequence information cannot confirm the identity of the shorter messages. [provided by RefSeq, Jul 2008]

COL5A3 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=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A3	NM_015719.4 link	c.850-131T>C		intron_variant	Intron 6 of 66	ENST00000264828.4	NP_056534.2	P25940
COL5A3	XM_011528042.3 link	c.847-131T>C		intron_variant	Intron 6 of 66		XP_011526344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A3	ENST00000264828.4 link	c.850-131T>C		intron_variant	Intron 6 of 66	1	NM_015719.4	ENSP00000264828.3		P25940

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56277

AN:

151774

Hom.:

10576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.389

AC:

189713

AN:

487316

Hom.:

37851

AF XY:

0.396

AC XY:

101389

AN XY:

256336

show subpopulations

African (AFR)

AF:

0.326

AC:

4216

AN:

12950

American (AMR)

AF:

0.398

AC:

7420

AN:

18632

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

5104

AN:

13712

East Asian (EAS)

AF:

0.349

AC:

10860

AN:

31100

South Asian (SAS)

AF:

0.512

AC:

23298

AN:

45462

European-Finnish (FIN)

AF:

0.399

AC:

17078

AN:

42854

Middle Eastern (MID)

AF:

0.367

AC:

724

AN:

1972

European-Non Finnish (NFE)

AF:

0.377

AC:

110730

AN:

293856

Other (OTH)

AF:

0.384

AC:

10283

AN:

26778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5319

10639

15958

21278

26597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.371

AC:

56328

AN:

151892

Hom.:

10590

Cov.:

AF XY:

0.374

AC XY:

27771

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.333

AC:

13802

AN:

41420

American (AMR)

AF:

0.391

AC:

5960

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1321

AN:

3470

East Asian (EAS)

AF:

0.328

AC:

1683

AN:

5124

South Asian (SAS)

AF:

0.531

AC:

2547

AN:

4798

European-Finnish (FIN)

AF:

0.396

AC:

4191

AN:

10586

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25609

AN:

67926

Other (OTH)

AF:

0.371

AC:

782

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1741

3482

5223

6964

8705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.378

Hom.:

22562

Bravo

AF:

0.361

Asia WGS

AF:

0.470

AC:

1634

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.52

(source)

DANN

Benign

0.73

PhyloP100

-0.37

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over