rs7333204

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.651+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,379,242 control chromosomes in the GnomAD database, including 47,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5499 hom., cov: 32)

Exomes 𝑓: 0.25 ( 42066 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.422

Publications

4 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=-0.86).

BP6

Variant 13-110209324-T-C is Benign according to our data. Variant chr13-110209324-T-C is described in ClinVar as Benign. ClinVar VariationId is 1293042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A1	NM_001845.6 link	c.651+68A>G		intron_variant	Intron 11 of 51	ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2 link	c.651+68A>G		intron_variant	Intron 11 of 24		NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10 link	c.651+68A>G		intron_variant	Intron 11 of 51	1	NM_001845.6	ENSP00000364979.4		P02462-1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40175

AN:

151768

Hom.:

5491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.0619

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.0458

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.253

AC:

310833

AN:

1227356

Hom.:

42066

AF XY:

0.253

AC XY:

157043

AN XY:

621300

show subpopulations

African (AFR)

AF:

0.268

AC:

7376

AN:

27544

American (AMR)

AF:

0.326

AC:

12377

AN:

38010

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

5608

AN:

23794

East Asian (EAS)

AF:

0.0321

AC:

1241

AN:

38688

South Asian (SAS)

AF:

0.227

AC:

17398

AN:

76680

European-Finnish (FIN)

AF:

0.312

AC:

16543

AN:

52944

Middle Eastern (MID)

AF:

0.257

AC:

1336

AN:

5200

European-Non Finnish (NFE)

AF:

0.259

AC:

236177

AN:

912068

Other (OTH)

AF:

0.244

AC:

12777

AN:

52428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

10995

21990

32984

43979

54974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7222

14444

21666

28888

36110

<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:

0.265

AC:

40219

AN:

151886

Hom.:

5499

Cov.:

AF XY:

0.266

AC XY:

19775

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.269

AC:

11164

AN:

41426

American (AMR)

AF:

0.320

AC:

4884

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

845

AN:

3470

East Asian (EAS)

AF:

0.0455

AC:

235

AN:

5166

South Asian (SAS)

AF:

0.213

AC:

1026

AN:

4810

European-Finnish (FIN)

AF:

0.321

AC:

3378

AN:

10524

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18077

AN:

67906

Other (OTH)

AF:

0.228

AC:

482

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1518

3035

4553

6070

7588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.259

Hom.:

7680

Bravo

AF:

0.262

Asia WGS

AF:

0.133

AC:

465

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

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.43

PhyloP100

-0.42

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