rs2166207

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_001845.6(COL4A1):c.615+59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,550,788 control chromosomes in the GnomAD database, including 104,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12663 hom., cov: 32)

Exomes 𝑓: 0.36 ( 91660 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.934

Publications

8 publications found

Variant links:

Genes affected

COL4A1 (HGNC:2202): (collagen type IV alpha 1 chain) This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

COL4A1 Gene-Disease associations (from GenCC):

brain small vessel disease 1 with or without ocular anomalies
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Orphanet, Genomics England PanelApp
autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics
microangiopathy and leukoencephalopathy, pontine, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
familial porencephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pontine autosomal dominant microangiopathy with leukoencephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinal arterial tortuosity
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL4A1 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=-0.85).

BP6

Variant 13-110209921-A-C is Benign according to our data. Variant chr13-110209921-A-C is described in ClinVar as Benign. ClinVar VariationId is 1272047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A1	NM_001845.6 link	c.615+59T>G		intron_variant	Intron 10 of 51	ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2 link	c.615+59T>G		intron_variant	Intron 10 of 24		NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 link	c.615+59T>G		intron_variant	Intron 10 of 51	1	NM_001845.6	ENSP00000364979.4		P02462-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60740

AN:

151962

Hom.:

12633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.374

AC:

93290

AN:

249314

AF XY:

0.365

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.357

AC:

499675

AN:

1398708

Hom.:

91660

Cov.:

AF XY:

0.355

AC XY:

248490

AN XY:

699872

show subpopulations

African (AFR)

AF:

0.509

AC:

16429

AN:

32258

American (AMR)

AF:

0.499

AC:

22274

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7608

AN:

25764

East Asian (EAS)

AF:

0.228

AC:

8981

AN:

39448

South Asian (SAS)

AF:

0.315

AC:

26813

AN:

84992

European-Finnish (FIN)

AF:

0.394

AC:

20993

AN:

53318

Middle Eastern (MID)

AF:

0.332

AC:

1879

AN:

5664

European-Non Finnish (NFE)

AF:

0.355

AC:

374090

AN:

1054346

Other (OTH)

AF:

0.354

AC:

20608

AN:

58274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15959

31919

47878

63838

79797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11706

23412

35118

46824

58530

<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:

0.400

AC:

60829

AN:

152080

Hom.:

12663

Cov.:

AF XY:

0.399

AC XY:

29669

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.493

AC:

20443

AN:

41482

American (AMR)

AF:

0.449

AC:

6864

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1045

AN:

3466

East Asian (EAS)

AF:

0.243

AC:

1257

AN:

5170

South Asian (SAS)

AF:

0.301

AC:

1448

AN:

4818

European-Finnish (FIN)

AF:

0.390

AC:

4135

AN:

10596

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.363

AC:

24645

AN:

67956

Other (OTH)

AF:

0.364

AC:

770

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1847

3694

5540

7387

9234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.373

Hom.:

2042

Bravo

AF:

0.409

Asia WGS

AF:

0.313

AC:

1087

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 26, 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

-0.85

CADD

Benign

4.4

(source)

DANN

Benign

0.61

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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