rs3747408

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 24511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108606846-G-A is described in Lovd as [Benign]. Variant chrX-108606846-G-A is described in Lovd as [Likely_benign].

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	P29400-2Q49AM6A7MBN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A5	ENST00000328300.11 link	c.2349G>A	p.Pro783Pro	synonymous_variant	Exon 29 of 53	1	NM_033380.3	ENSP00000331902.7	P29400-2
COL4A5	ENST00000483338.1 link	c.1173G>A	p.Pro391Pro	synonymous_variant	Exon 13 of 20	1		ENSP00000495685.1	Q49AM6
COL4A5	ENST00000361603.7 link	c.2349G>A	p.Pro783Pro	synonymous_variant	Exon 29 of 51	2		ENSP00000354505.2	P29400-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

11569

AN:

110925

Hom.:

1298

Cov.:

AF XY:

0.0958

AC XY:

3179

AN XY:

33185

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

GnomAD3 exomes

AF:

0.0454

AC:

8307

AN:

183121

Hom.:

698

AF XY:

0.0344

AC XY:

2326

AN XY:

67703

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 SAS exome

AF:

0.0172

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

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.0470

Gnomad4 ASJ exome

AF:

0.00361

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.0397

GnomAD4 genome

AF:

0.104

AC:

11579

AN:

110972

Hom.:

1298

Cov.:

AF XY:

0.0960

AC XY:

3192

AN XY:

33242

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.0565

Gnomad4 ASJ

AF:

0.00303

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.000168

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.0908

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

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

- -

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). -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

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

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over