rs10203363

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000092.5(COL4A4):c.3594G>A(p.Gly1198Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,611,530 control chromosomes in the GnomAD database, including 160,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16806 hom., cov: 32)

Exomes 𝑓: 0.44 ( 143985 hom. )

Consequence

COL4A4
NM_000092.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0340

Publications

27 publications found

Variant links:

Genes affected

COL4A4 (HGNC:2206): (collagen type IV alpha 4 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]

COL4A4 Gene-Disease associations (from GenCC):

autosomal recessive Alport syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Myriad Women’s Health, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Alport syndrome
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
hematuria, benign familial, 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
autosomal dominant Alport syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL4A4 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=-0.52).

BP6

Variant 2-227032260-C-T is Benign according to our data. Variant chr2-227032260-C-T is described in ClinVar as Benign. ClinVar VariationId is 255031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.034 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000092.5. 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
	COL4A4	NM_000092.5	MANE Select	c.3594G>A	p.Gly1198Gly	synonymous	Exon 39 of 48	NP_000083.3	P53420

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A4	ENST00000396625.5	TSL:5 MANE Select	c.3594G>A	p.Gly1198Gly	synonymous	Exon 39 of 48	ENSP00000379866.3	P53420

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70896

AN:

151866

Hom.:

16775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.436

GnomAD2 exomes

AF:

0.473

AC:

117270

AN:

248086

AF XY:

0.471

show subpopulations

Gnomad AFR exome

AF:

0.535

Gnomad AMR exome

AF:

0.533

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.441

AC:

643314

AN:

1459546

Hom.:

143985

Cov.:

AF XY:

0.443

AC XY:

321587

AN XY:

726158

show subpopulations

African (AFR)

AF:

0.529

AC:

17671

AN:

33428

American (AMR)

AF:

0.528

AC:

23534

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

13621

AN:

26098

East Asian (EAS)

AF:

0.404

AC:

16012

AN:

39682

South Asian (SAS)

AF:

0.569

AC:

49069

AN:

86208

European-Finnish (FIN)

AF:

0.498

AC:

26581

AN:

53388

Middle Eastern (MID)

AF:

0.398

AC:

2292

AN:

5758

European-Non Finnish (NFE)

AF:

0.421

AC:

467759

AN:

1110078

Other (OTH)

AF:

0.444

AC:

26775

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

20346

40693

61039

81386

101732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14494

28988

43482

57976

72470

<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:

0.467

AC:

70971

AN:

151984

Hom.:

16806

Cov.:

AF XY:

0.469

AC XY:

34810

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.530

AC:

21974

AN:

41454

American (AMR)

AF:

0.469

AC:

7161

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1730

AN:

3462

East Asian (EAS)

AF:

0.389

AC:

2003

AN:

5152

South Asian (SAS)

AF:

0.564

AC:

2711

AN:

4806

European-Finnish (FIN)

AF:

0.493

AC:

5207

AN:

10562

Middle Eastern (MID)

AF:

0.401

AC:

117

AN:

292

European-Non Finnish (NFE)

AF:

0.424

AC:

28793

AN:

67962

Other (OTH)

AF:

0.430

AC:

907

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1920

3839

5759

7678

9598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.445

Hom.:

8824

Bravo

AF:

0.468

Asia WGS

AF:

0.482

AC:

1679

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (3)

Alport syndrome (2)

Autosomal recessive Alport syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.9

(source)

DANN

Benign

0.56

PhyloP100

-0.034

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

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