rs7884085

Variant names:

Variant summary

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

The NM_033380.3(COL4A5):c.2055T>C(p.Leu685Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,152,504 control chromosomes in the GnomAD database, including 2,670 homozygotes. There are 7,507 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 ( 1308 hom., 3012 hem., cov: 22)

Exomes 𝑓: 0.016 ( 1362 hom. 4495 hem. )

Consequence

COL4A5
NM_033380.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.786

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-108601898-T-C is Benign according to our data. Variant chrX-108601898-T-C is described in ClinVar as Benign. ClinVar VariationId is 24481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.786 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3 link	c.2055T>C	p.Leu685Leu	synonymous_variant	Exon 27 of 53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
COL4A5	ENST00000328300.11 link	c.2055T>C	p.Leu685Leu	synonymous_variant	Exon 27 of 53	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338.1 link	c.879T>C	p.Leu293Leu	synonymous_variant	Exon 11 of 20	1		ENSP00000495685.1
COL4A5	ENST00000361603.7 link	c.2055T>C	p.Leu685Leu	synonymous_variant	Exon 27 of 51	2		ENSP00000354505.2

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

11409

AN:

110806

Hom.:

1308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.00303

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.000166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.0889

GnomAD2 exomes

AF:

0.0447

AC:

5777

AN:

129141

AF XY:

0.0332

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.0427

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0157

AC:

16321

AN:

1041646

Hom.:

1362

Cov.:

AF XY:

0.0137

AC XY:

4495

AN XY:

327162

show subpopulations

African (AFR)

AF:

0.336

AC:

8403

AN:

24977

American (AMR)

AF:

0.0466

AC:

1385

AN:

29715

Ashkenazi Jewish (ASJ)

AF:

0.00372

AC:

AN:

18530

East Asian (EAS)

AF:

0.121

AC:

3424

AN:

28376

South Asian (SAS)

AF:

0.0145

AC:

724

AN:

50014

European-Finnish (FIN)

AF:

0.000183

AC:

AN:

38280

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

3951

European-Non Finnish (NFE)

AF:

0.000601

AC:

483

AN:

803842

Other (OTH)

AF:

0.0405

AC:

1780

AN:

43961

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

407

815

1222

1630

2037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.103

AC:

11420

AN:

110858

Hom.:

1308

Cov.:

AF XY:

0.0909

AC XY:

3012

AN XY:

33130

show subpopulations

African (AFR)

AF:

0.334

AC:

10075

AN:

30150

American (AMR)

AF:

0.0557

AC:

587

AN:

10546

Ashkenazi Jewish (ASJ)

AF:

0.00303

AC:

AN:

2641

East Asian (EAS)

AF:

0.142

AC:

494

AN:

3476

South Asian (SAS)

AF:

0.0207

AC:

AN:

2613

European-Finnish (FIN)

AF:

0.000166

AC:

AN:

6041

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

52978

Other (OTH)

AF:

0.0878

AC:

133

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

301

602

902

1203

1504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.129

Hom.:

1736

Bravo

AF:

0.121

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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.Leu685Leu in exon 27 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 40.39% (1404/3476) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs7884085). -

Apr 07, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Mar 03, 2015

GeneDx

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

- -

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

-0.74

CADD

Benign

6.7

(source)

DANN

Benign

0.75

PhyloP100

-0.79

Mutation Taster

=99/1

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