Genetic Variant NM_001846.4:c.1432+77A>G (chr13-110457512-A-G) – 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.1432+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 847,884 control chromosomes in the GnomAD database, including 137,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25659 hom., cov: 32)

Exomes 𝑓: 0.55 ( 111857 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.39

Publications

10 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-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

COL4A2-AS2 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=-0.92).

BP6

Variant 13-110457512-A-G is Benign according to our data. Variant chr13-110457512-A-G is described in ClinVar as Benign. ClinVar VariationId is 1249370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.1432+77A>G		intron_variant	Intron 21 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS2	NR_171022.1 link	n.561+13T>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 link	c.1432+77A>G		intron_variant	Intron 21 of 47	5	NM_001846.4	ENSP00000353654.5		P08572

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86896

AN:

151944

Hom.:

25634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.520

AC:

97398

AN:

187482

AF XY:

0.524

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.557

GnomAD4 exome

AF:

0.554

AC:

385330

AN:

695822

Hom.:

111857

Cov.:

AF XY:

0.553

AC XY:

205069

AN XY:

370836

show subpopulations

African (AFR)

AF:

0.632

AC:

11577

AN:

18306

American (AMR)

AF:

0.399

AC:

15412

AN:

38594

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

13903

AN:

20854

East Asian (EAS)

AF:

0.177

AC:

6022

AN:

33944

South Asian (SAS)

AF:

0.478

AC:

32005

AN:

66960

European-Finnish (FIN)

AF:

0.444

AC:

22408

AN:

50442

Middle Eastern (MID)

AF:

0.688

AC:

2966

AN:

4308

European-Non Finnish (NFE)

AF:

0.611

AC:

261080

AN:

427534

Other (OTH)

AF:

0.572

AC:

19957

AN:

34880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

8742

17483

26225

34966

43708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3010

6020

9030

12040

15050

<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:

0.572

AC:

86971

AN:

152062

Hom.:

25659

Cov.:

AF XY:

0.559

AC XY:

41553

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.628

AC:

26047

AN:

41494

American (AMR)

AF:

0.489

AC:

7480

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

2357

AN:

3470

East Asian (EAS)

AF:

0.225

AC:

1159

AN:

5142

South Asian (SAS)

AF:

0.458

AC:

2206

AN:

4818

European-Finnish (FIN)

AF:

0.430

AC:

4552

AN:

10576

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41117

AN:

67956

Other (OTH)

AF:

0.578

AC:

1220

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1867

3733

5600

7466

9333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<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:

0.594

Hom.:

6737

Bravo

AF:

0.578

Asia WGS

AF:

0.374

AC:

1304

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

-0.92

CADD

Benign

0.24

(source)

DANN

Benign

0.30

PhyloP100

-1.4

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