rs3747408

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_033380.3(COL4A5):c.2349G>A(p.Pro783Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,208,260 control chromosomes in the GnomAD database, including 2,715 homozygotes. There are 8,298 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1298 hom., 3192 hem., cov: 22)

Exomes 𝑓: 0.016 ( 1417 hom. 5106 hem. )

Consequence

COL4A5
NM_033380.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0140

Publications

7 publications found

Variant links:

Genes affected

COL4A5 (HGNC:2207): (collagen type IV alpha 5 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

COL4A5 Gene-Disease associations (from GenCC):

Alport syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, G2P
X-linked Alport syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)

COL4A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant X-108606846-G-A is Benign according to our data. Variant chrX-108606846-G-A is described in ClinVar as Benign. ClinVar VariationId is 24511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3 link	c.2349G>A	p.Pro783Pro	synonymous_variant	Exon 29 of 53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
COL4A5	ENST00000328300.11 link	c.2349G>A	p.Pro783Pro	synonymous_variant	Exon 29 of 53	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338.1 link	c.1173G>A	p.Pro391Pro	synonymous_variant	Exon 13 of 20	1		ENSP00000495685.1
COL4A5	ENST00000361603.7 link	c.2349G>A	p.Pro783Pro	synonymous_variant	Exon 29 of 51	2		ENSP00000354505.2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

11569

AN:

110925

Hom.:

1298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0568

Gnomad ASJ

AF:

0.00303

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.0919

GnomAD2 exomes

AF:

0.0454

AC:

8307

AN:

183121

AF XY:

0.0344

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.0438

Gnomad ASJ exome

AF:

0.00374

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000845

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0161

AC:

17647

AN:

1097288

Hom.:

1417

Cov.:

AF XY:

0.0141

AC XY:

5106

AN XY:

362670

show subpopulations

African (AFR)

AF:

0.340

AC:

8984

AN:

26388

American (AMR)

AF:

0.0470

AC:

1654

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00361

AC:

AN:

19379

East Asian (EAS)

AF:

0.124

AC:

3730

AN:

30201

South Asian (SAS)

AF:

0.0150

AC:

814

AN:

54122

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.000607

AC:

511

AN:

841270

Other (OTH)

AF:

0.0397

AC:

1829

AN:

46058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

598

1196

1794

2392

2990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.104

AC:

11579

AN:

110972

Hom.:

1298

Cov.:

AF XY:

0.0960

AC XY:

3192

AN XY:

33242

show subpopulations

African (AFR)

AF:

0.337

AC:

10204

AN:

30313

American (AMR)

AF:

0.0565

AC:

591

AN:

10458

Ashkenazi Jewish (ASJ)

AF:

0.00303

AC:

AN:

2641

East Asian (EAS)

AF:

0.146

AC:

511

AN:

3494

South Asian (SAS)

AF:

0.0212

AC:

AN:

2640

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

5958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

53054

Other (OTH)

AF:

0.0908

AC:

138

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

292

584

876

1168

1460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0452

Hom.:

503

Bravo

AF:

0.121

EpiCase

AF:

0.000818

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro783Pro in exon 29 of COL4A5: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 39.48% (396/1003) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs3747408). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

X-linked Alport syndrome

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 21, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

-0.33

CADD

Benign

7.1

(source)

DANN

Benign

0.66

PhyloP100

0.014

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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