rs3832900

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001845.6(COL4A1):c.468+15_468+19delATTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,609,704 control chromosomes in the GnomAD database, including 1,293 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 306 hom., cov: 32)

Exomes 𝑓: 0.022 ( 987 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.06

Publications

3 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: Genomics England PanelApp, Orphanet, Ambry Genetics, G2P, PanelApp Australia
autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, 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 -16 ACMG points.

BP6

Variant 13-110211627-CAAAAT-C is Benign according to our data. Variant chr13-110211627-CAAAAT-C is described in ClinVar as Benign. ClinVar VariationId is 258258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 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.468+15_468+19delATTTT		intron	N/A	NP_001836.3	P02462-1
	COL4A1	NM_001303110.2		c.468+15_468+19delATTTT		intron	N/A	NP_001290039.1	P02462-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.468+15_468+19delATTTT	intron	N/A	ENSP00000364979.4	P02462-1
COL4A1	ENST00000543140.6	TSL:1	c.468+15_468+19delATTTT	intron	N/A	ENSP00000443348.1	P02462-2
COL4A1	ENST00000650424.2		c.468+15_468+19delATTTT	intron	N/A	ENSP00000497477.2	A0A3B3ISV3

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7157

AN:

152026

Hom.:

301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0608

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0962

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00520

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0384

AC:

9526

AN:

248090

AF XY:

0.0324

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.0953

Gnomad FIN exome

AF:

0.00560

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0216

AC:

31492

AN:

1457560

Hom.:

987

AF XY:

0.0205

AC XY:

14868

AN XY:

725078

show subpopulations

African (AFR)

AF:

0.116

AC:

3867

AN:

33266

American (AMR)

AF:

0.104

AC:

4587

AN:

44028

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

305

AN:

26036

East Asian (EAS)

AF:

0.107

AC:

4248

AN:

39644

South Asian (SAS)

AF:

0.00570

AC:

486

AN:

85278

European-Finnish (FIN)

AF:

0.00608

AC:

322

AN:

52928

Middle Eastern (MID)

AF:

0.0278

AC:

159

AN:

5728

European-Non Finnish (NFE)

AF:

0.0144

AC:

15999

AN:

1110410

Other (OTH)

AF:

0.0252

AC:

1519

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

1322

2643

3965

5286

6608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.0472

AC:

7175

AN:

152144

Hom.:

306

Cov.:

AF XY:

0.0459

AC XY:

3413

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.109

AC:

4523

AN:

41470

American (AMR)

AF:

0.0608

AC:

930

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3470

East Asian (EAS)

AF:

0.0970

AC:

503

AN:

5186

South Asian (SAS)

AF:

0.00704

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00520

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

982

AN:

68012

Other (OTH)

AF:

0.0492

AC:

104

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

326

653

979

1306

1632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0295

Hom.:

Bravo

AF:

0.0580

Asia WGS

AF:

0.0770

AC:

266

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

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

not specified (2)

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

Porencephalic cyst (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over