Genetic Variant COL4A2:c.4139-41G>A (chr13-110503806-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001846.4(COL4A2):c.4139-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,609,432 control chromosomes in the GnomAD database, including 110,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11531 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98822 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.01

Publications

12 publications found

Variant links:

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

COL4A2 links:

COL4A2-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

COL4A2-AS1 links:

ENSG00000289010 (HGNC:):

ENSG00000289010 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=-0.8).

BP6

Variant 13-110503806-G-A is Benign according to our data. Variant chr13-110503806-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.4139-41G>A		intron_variant	Intron 43 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS1	NR_046583.1 link	n.187-878C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 link	c.4139-41G>A		intron_variant	Intron 43 of 47	5	NM_001846.4	ENSP00000353654.5		P08572

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58431

AN:

151852

Hom.:

11520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.376

GnomAD2 exomes

AF:

0.348

AC:

86375

AN:

248350

AF XY:

0.354

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.364

AC:

529898

AN:

1457462

Hom.:

98822

Cov.:

AF XY:

0.365

AC XY:

264575

AN XY:

725280

show subpopulations

African (AFR)

AF:

0.468

AC:

15587

AN:

33330

American (AMR)

AF:

0.232

AC:

10324

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

9363

AN:

26078

East Asian (EAS)

AF:

0.182

AC:

7216

AN:

39674

South Asian (SAS)

AF:

0.376

AC:

32328

AN:

86078

European-Finnish (FIN)

AF:

0.420

AC:

22410

AN:

53374

Middle Eastern (MID)

AF:

0.412

AC:

2365

AN:

5734

European-Non Finnish (NFE)

AF:

0.368

AC:

407997

AN:

1108510

Other (OTH)

AF:

0.371

AC:

22308

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

14466

28932

43399

57865

72331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12850

25700

38550

51400

64250

<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:

0.385

AC:

58471

AN:

151970

Hom.:

11531

Cov.:

AF XY:

0.384

AC XY:

28534

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.459

AC:

19035

AN:

41450

American (AMR)

AF:

0.309

AC:

4728

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1224

AN:

3464

East Asian (EAS)

AF:

0.197

AC:

1016

AN:

5146

South Asian (SAS)

AF:

0.387

AC:

1869

AN:

4830

European-Finnish (FIN)

AF:

0.415

AC:

4396

AN:

10584

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.369

AC:

25050

AN:

67898

Other (OTH)

AF:

0.373

AC:

786

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1851

3702

5552

7403

9254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.383

Hom.:

2598

Bravo

AF:

0.375

Asia WGS

AF:

0.296

AC:

1031

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

(source)

DANN

Benign

0.55

PhyloP100

1.0

PromoterAI

-0.047

Neutral

(source)

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