rs1562173

Variant names:

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.2968+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,591,596 control chromosomes in the GnomAD database, including 104,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8845 hom., cov: 32)

Exomes 𝑓: 0.36 ( 95458 hom. )

Consequence

COL4A1
NM_001845.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.17

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 13-110176575-G-A is Benign according to our data. Variant chr13-110176575-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 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.2968+51C>T		intron	N/A	NP_001836.3	P02462-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.2968+51C>T	intron	N/A	ENSP00000364979.4	P02462-1
COL4A1	ENST00000650424.2		c.2968+51C>T	intron	N/A	ENSP00000497477.2	A0A3B3ISV3
COL4A1	ENST00000933608.1		c.2968+51C>T	intron	N/A	ENSP00000603667.1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51589

AN:

151858

Hom.:

8832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.352

GnomAD2 exomes

AF:

0.355

AC:

88832

AN:

250068

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.364

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.362

AC:

520724

AN:

1439620

Hom.:

95458

Cov.:

AF XY:

0.362

AC XY:

259647

AN XY:

717530

show subpopulations

African (AFR)

AF:

0.269

AC:

8908

AN:

33080

American (AMR)

AF:

0.392

AC:

17490

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

8277

AN:

25998

East Asian (EAS)

AF:

0.268

AC:

10600

AN:

39596

South Asian (SAS)

AF:

0.365

AC:

31327

AN:

85852

European-Finnish (FIN)

AF:

0.352

AC:

18804

AN:

53352

Middle Eastern (MID)

AF:

0.263

AC:

1506

AN:

5722

European-Non Finnish (NFE)

AF:

0.369

AC:

402710

AN:

1091758

Other (OTH)

AF:

0.354

AC:

21102

AN:

59606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17999

35999

53998

71998

89997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12636

25272

37908

50544

63180

<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:

0.340

AC:

51642

AN:

151976

Hom.:

8845

Cov.:

AF XY:

0.340

AC XY:

25253

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.277

AC:

11498

AN:

41458

American (AMR)

AF:

0.361

AC:

5517

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1182

AN:

3470

East Asian (EAS)

AF:

0.301

AC:

1551

AN:

5156

South Asian (SAS)

AF:

0.364

AC:

1753

AN:

4818

European-Finnish (FIN)

AF:

0.350

AC:

3690

AN:

10556

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.369

AC:

25094

AN:

67932

Other (OTH)

AF:

0.357

AC:

754

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1753

3507

5260

7014

8767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.347

Hom.:

2126

Bravo

AF:

0.337

Asia WGS

AF:

0.361

AC:

1255

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.050

(source)

DANN

Benign

0.34

PhyloP100

-4.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over