Genetic Variant COL6A5:c.2993-98T>G (chr3-130394792-T-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_001278298.2(COL6A5):c.2993-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 806,690 control chromosomes in the GnomAD database, including 32,992 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 0.29 ( 7342 hom., cov: 32)

Exomes 𝑓: 0.25 ( 25650 hom. )

Consequence

COL6A5
NM_001278298.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

5 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:

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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=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COL6A5	NM_001278298.2 link	c.2993-98T>G	intron_variant	Intron 7 of 40	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7 link	c.2993-98T>G	intron_variant	Intron 7 of 39		NP_694996.5
COL6A5	NR_022012.3 link	n.3331-98T>G	intron_variant	Intron 7 of 41

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL6A5	ENST00000373157.9 link	c.2993-98T>G	intron_variant	Intron 7 of 40	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11 link	n.2993-98T>G	intron_variant	Intron 7 of 41	1		ENSP00000309762.7
COL6A5	ENST00000512836.6 link	c.2993-98T>G	intron_variant	Intron 7 of 39	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43896

AN:

151986

Hom.:

7316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.282

GnomAD4 exome

AF:

0.252

AC:

164968

AN:

654586

Hom.:

25650

AF XY:

0.254

AC XY:

86642

AN XY:

340626

show subpopulations

African (AFR)

AF:

0.392

AC:

6252

AN:

15966

American (AMR)

AF:

0.409

AC:

7985

AN:

19530

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

5012

AN:

17522

East Asian (EAS)

AF:

0.673

AC:

21487

AN:

31918

South Asian (SAS)

AF:

0.349

AC:

18342

AN:

52512

European-Finnish (FIN)

AF:

0.172

AC:

5909

AN:

34360

Middle Eastern (MID)

AF:

0.264

AC:

659

AN:

2494

European-Non Finnish (NFE)

AF:

0.203

AC:

90633

AN:

447268

Other (OTH)

AF:

0.263

AC:

8689

AN:

33016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5817

11634

17452

23269

29086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2050

4100

6150

8200

10250

<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:

0.289

AC:

43973

AN:

152104

Hom.:

7342

Cov.:

AF XY:

0.292

AC XY:

21744

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.393

AC:

16283

AN:

41460

American (AMR)

AF:

0.361

AC:

5513

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1005

AN:

3472

East Asian (EAS)

AF:

0.608

AC:

3143

AN:

5170

South Asian (SAS)

AF:

0.357

AC:

1722

AN:

4818

European-Finnish (FIN)

AF:

0.166

AC:

1756

AN:

10586

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13675

AN:

67994

Other (OTH)

AF:

0.289

AC:

609

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1496

2991

4487

5982

7478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.235

Hom.:

19241

Bravo

AF:

0.311

Asia WGS

AF:

0.486

AC:

1689

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.40

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

Computational scores

Splicing

Publications

Other links and lift over