chr13-110181355-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001845.6(COL4A1):c.2130G>A(p.Pro710Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,612,120 control chromosomes in the GnomAD database, including 103,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8380 hom., cov: 31)

Exomes 𝑓: 0.36 ( 95125 hom. )

Consequence

COL4A1
NM_001845.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -5.01

Publications

23 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: Ambry Genetics, Orphanet, G2P, Genomics England PanelApp
autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 13-110181355-C-T is Benign according to our data. Variant chr13-110181355-C-T is described in ClinVar as Benign. ClinVar VariationId is 258249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001845.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	NM_001845.6	MANE Select	c.2130G>A	p.Pro710Pro	synonymous	Exon 29 of 52	NP_001836.3	P02462-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.2130G>A	p.Pro710Pro	synonymous	Exon 29 of 52	ENSP00000364979.4	P02462-1
COL4A1	ENST00000650424.2		c.2130G>A	p.Pro710Pro	synonymous	Exon 29 of 52	ENSP00000497477.2	A0A3B3ISV3
COL4A1	ENST00000933608.1		c.2130G>A	p.Pro710Pro	synonymous	Exon 29 of 51	ENSP00000603667.1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49626

AN:

151264

Hom.:

8368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.343

GnomAD2 exomes

AF:

0.351

AC:

87621

AN:

249938

AF XY:

0.352

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.359

AC:

523824

AN:

1460740

Hom.:

95125

Cov.:

AF XY:

0.359

AC XY:

261125

AN XY:

726648

show subpopulations

African (AFR)

AF:

0.232

AC:

7755

AN:

33468

American (AMR)

AF:

0.388

AC:

17309

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8351

AN:

26118

East Asian (EAS)

AF:

0.257

AC:

10183

AN:

39670

South Asian (SAS)

AF:

0.373

AC:

32146

AN:

86174

European-Finnish (FIN)

AF:

0.356

AC:

18972

AN:

53362

Middle Eastern (MID)

AF:

0.266

AC:

1527

AN:

5750

European-Non Finnish (NFE)

AF:

0.366

AC:

406517

AN:

1111226

Other (OTH)

AF:

0.349

AC:

21064

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

17618

35236

52854

70472

88090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12868

25736

38604

51472

64340

<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:

0.328

AC:

49665

AN:

151380

Hom.:

8380

Cov.:

AF XY:

0.329

AC XY:

24300

AN XY:

73876

show subpopulations

African (AFR)

AF:

0.239

AC:

9862

AN:

41248

American (AMR)

AF:

0.356

AC:

5431

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3468

East Asian (EAS)

AF:

0.293

AC:

1502

AN:

5118

South Asian (SAS)

AF:

0.371

AC:

1770

AN:

4776

European-Finnish (FIN)

AF:

0.353

AC:

3684

AN:

10432

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.367

AC:

24902

AN:

67804

Other (OTH)

AF:

0.349

AC:

730

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1674

3347

5021

6694

8368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.345

Hom.:

12461

Bravo

AF:

0.324

Asia WGS

AF:

0.354

AC:

1230

AN:

3478

EpiCase

AF:

0.353

EpiControl

AF:

0.353

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Brain small vessel disease 1 with or without ocular anomalies (2)

not provided (2)

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.74

(source)

DANN

Benign

0.41

PhyloP100

-5.0

Mutation Taster

=96/4

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over