rs73868680

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001278298.2(COL6A5):c.7765G>A(p.Ala2589Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,468,390 control chromosomes in the GnomAD database, including 4,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 1208 hom., cov: 23)

Exomes 𝑓: 0.065 ( 3727 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.413

Publications

7 publications found

Variant links:

Genes affected

COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

COL6A5 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 (MetaRNN=0.006091118).

BP6

Variant 3-130471872-G-A is Benign according to our data. Variant chr3-130471872-G-A is described in ClinVar as Benign. ClinVar VariationId is 402555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2 link	c.7765G>A	p.Ala2589Thr	missense_variant	Exon 40 of 41	ENST00000373157.9	NP_001265227.1	A8TX70H0Y393
COL6A5	NR_022012.3 link	n.8103G>A		non_coding_transcript_exon_variant	Exon 40 of 42
COL6A5	NM_153264.7 link	c.7574+905G>A		intron_variant	Intron 39 of 39		NP_694996.5	A8TX70-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A5	ENST00000373157.9 link	c.7765G>A	p.Ala2589Thr	missense_variant	Exon 40 of 41	2	NM_001278298.2	ENSP00000362250.5	H0Y393
COL6A5	ENST00000312481.11 link	n.7765G>A		non_coding_transcript_exon_variant	Exon 40 of 42	1		ENSP00000309762.7	A8TX70-1
COL6A5	ENST00000512482.1 link	c.1270G>A	p.Ala424Thr	missense_variant	Exon 5 of 6	5		ENSP00000424968.1	H0Y9T2
COL6A5	ENST00000512836.6 link	c.7574+905G>A		intron_variant	Intron 39 of 39	2		ENSP00000422898.2	A8TX70-2H0Y935

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

15824

AN:

85468

Hom.:

1203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.0741

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0476

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.162

GnomAD2 exomes

AF:

0.164

AC:

11817

AN:

72030

AF XY:

0.164

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0716

Gnomad FIN exome

AF:

0.0461

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.0647

AC:

89457

AN:

1382786

Hom.:

3727

Cov.:

AF XY:

0.0657

AC XY:

44850

AN XY:

682376

show subpopulations

African (AFR)

AF:

0.217

AC:

6843

AN:

31534

American (AMR)

AF:

0.122

AC:

4348

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.0618

AC:

1553

AN:

25148

East Asian (EAS)

AF:

0.0438

AC:

1565

AN:

35698

South Asian (SAS)

AF:

0.118

AC:

9319

AN:

79200

European-Finnish (FIN)

AF:

0.0210

AC:

710

AN:

33884

Middle Eastern (MID)

AF:

0.0857

AC:

487

AN:

5682

European-Non Finnish (NFE)

AF:

0.0558

AC:

60149

AN:

1078110

Other (OTH)

AF:

0.0775

AC:

4483

AN:

57844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

4842

9685

14527

19370

24212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2466

4932

7398

9864

12330

<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:

0.185

AC:

15859

AN:

85604

Hom.:

1208

Cov.:

AF XY:

0.180

AC XY:

7537

AN XY:

41830

show subpopulations

African (AFR)

AF:

0.243

AC:

9075

AN:

37366

American (AMR)

AF:

0.169

AC:

1469

AN:

8692

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

205

AN:

1560

East Asian (EAS)

AF:

0.0742

AC:

301

AN:

4054

South Asian (SAS)

AF:

0.185

AC:

544

AN:

2940

European-Finnish (FIN)

AF:

0.0476

AC:

191

AN:

4010

Middle Eastern (MID)

AF:

0.200

AC:

AN:

130

European-Non Finnish (NFE)

AF:

0.148

AC:

3735

AN:

25234

Other (OTH)

AF:

0.162

AC:

201

AN:

1240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

674

1348

2023

2697

3371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.147

Hom.:

410

Bravo

AF:

0.116

ExAC

AF:

0.159

AC:

1354

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

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

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.45

PhyloP100

0.41

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.67

.;N;N

REVEL

Benign

0.18

Sift

Benign

0.13

.;T;T

Sift4G

Uncertain

0.023

D;T;T

Vest4

0.080

MPC

0.051

ClinPred

0.0047

GERP RS

1.2

gMVP

0.054

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over