rs2272945

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_033380.3(COL4A5):c.1095G>C(p.Gly365Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,205,928 control chromosomes in the GnomAD database, including 2,808 homozygotes. There are 8,319 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G365G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1347 hom., 3194 hem., cov: 22)

Exomes 𝑓: 0.016 ( 1461 hom. 5125 hem. )

Consequence

COL4A5
NM_033380.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.895

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-108586677-G-C is Benign according to our data. Variant chrX-108586677-G-C is described in ClinVar as Benign. ClinVar VariationId is 24365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.895 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3 link	c.1095G>C	p.Gly365Gly	synonymous_variant	Exon 19 of 53	ENST00000328300.11	NP_203699.1	P29400-2Q49AM6A7MBN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A5	ENST00000328300.11 link	c.1095G>C	p.Gly365Gly	synonymous_variant	Exon 19 of 53	1	NM_033380.3	ENSP00000331902.7	P29400-2
COL4A5	ENST00000483338.1 link	c.-82G>C		5_prime_UTR_variant	Exon 3 of 20	1		ENSP00000495685.1	Q49AM6
COL4A5	ENST00000361603.7 link	c.1095G>C	p.Gly365Gly	synonymous_variant	Exon 19 of 51	2		ENSP00000354505.2	P29400-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

11721

AN:

110336

Hom.:

1347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0563

Gnomad ASJ

AF:

0.00304

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.0894

GnomAD2 exomes

AF:

0.0458

AC:

8396

AN:

183258

AF XY:

0.0344

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.0437

Gnomad ASJ exome

AF:

0.00374

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000843

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0162

AC:

17771

AN:

1095540

Hom.:

1461

Cov.:

AF XY:

0.0142

AC XY:

5125

AN XY:

361180

show subpopulations

African (AFR)

AF:

0.346

AC:

9103

AN:

26327

American (AMR)

AF:

0.0470

AC:

1654

AN:

35165

Ashkenazi Jewish (ASJ)

AF:

0.00362

AC:

AN:

19341

East Asian (EAS)

AF:

0.124

AC:

3730

AN:

30185

South Asian (SAS)

AF:

0.0151

AC:

816

AN:

54015

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

40526

Middle Eastern (MID)

AF:

0.0119

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.000605

AC:

508

AN:

839867

Other (OTH)

AF:

0.0399

AC:

1834

AN:

45989

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

573

1145

1718

2290

2863

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:

0.106

AC:

11733

AN:

110388

Hom.:

1347

Cov.:

AF XY:

0.0976

AC XY:

3194

AN XY:

32734

show subpopulations

African (AFR)

AF:

0.344

AC:

10381

AN:

30195

American (AMR)

AF:

0.0560

AC:

582

AN:

10384

Ashkenazi Jewish (ASJ)

AF:

0.00304

AC:

AN:

2635

East Asian (EAS)

AF:

0.144

AC:

506

AN:

3502

South Asian (SAS)

AF:

0.0208

AC:

AN:

2602

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

5960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00131

AC:

AN:

52712

Other (OTH)

AF:

0.0883

AC:

132

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

297

594

892

1189

1486

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:

0.0156

Hom.:

102

Bravo

AF:

0.123

EpiCase

AF:

0.000928

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2021

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

Significance:Benign

Review Status:criteria provided, single submitter

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.Gly365Gly in exon 19 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 40.08% (402/1003) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs2272945). -

not provided

Benign:3

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

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 26, 2021

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

6.2

(source)

DANN

Benign

0.51

PhyloP100

-0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over