rs1006269

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033380.3(COL4A5):c.2768-11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,207,751 control chromosomes in the GnomAD database, including 8,060 homozygotes. There are 50,294 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 ( 637 hom., 3543 hem., cov: 23)

Exomes 𝑓: 0.13 ( 7423 hom. 46751 hem. )

Consequence

COL4A5
NM_033380.3 intron

Scores

Splicing: ADA: 0.00003877

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.145

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-108622665-A-G is Benign according to our data. Variant chrX-108622665-A-G is described in ClinVar as [Benign]. Clinvar id is 24563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108622665-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3 link	c.2768-11A>G		intron_variant	Intron 32 of 52	ENST00000328300.11	NP_203699.1	P29400-2Q49AM6A7MBN3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A5	ENST00000328300.11 link	c.2768-11A>G	intron_variant	Intron 32 of 52	1	NM_033380.3	ENSP00000331902.7	P29400-2
COL4A5	ENST00000483338.1 link	c.1592-11A>G	intron_variant	Intron 16 of 19	1		ENSP00000495685.1	Q49AM6
COL4A5	ENST00000361603.7 link	c.2768-11A>G	intron_variant	Intron 32 of 50	2		ENSP00000354505.2	P29400-1
COL4A5	ENST00000505728.1 link	c.-13A>G	upstream_gene_variant		3		ENSP00000424137.1	H0Y9H0

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

11326

AN:

111943

Hom.:

638

Cov.:

AF XY:

0.104

AC XY:

3539

AN XY:

34131

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.0763

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.0696

Gnomad MID

AF:

0.0763

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0979

GnomAD3 exomes

AF:

0.161

AC:

29492

AN:

182713

Hom.:

2311

AF XY:

0.159

AC XY:

10721

AN XY:

67427

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.0744

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.126

AC:

138272

AN:

1095759

Hom.:

7423

Cov.:

AF XY:

0.129

AC XY:

46751

AN XY:

361757

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.0754

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.0819

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.101

AC:

11324

AN:

111992

Hom.:

637

Cov.:

AF XY:

0.104

AC XY:

3543

AN XY:

34190

show subpopulations

Gnomad4 AFR

AF:

0.0173

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.0763

Gnomad4 EAS

AF:

0.327

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.0696

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.0954

Alfa

AF:

0.113

Hom.:

3810

Bravo

AF:

0.109

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 17, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 25, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.2768-11A>G in intron 32A of COL4A5: This variant is not expected to have clini cal significance because it has been identified in 32.6% (8823/27099) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinsti tute.org/; dbSNP rs1006269). -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 37% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 34. Only high quality variants are reported. -

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

X-linked Alport syndrome

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 04, 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

-0.81

CADD

Benign

4.9

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000039

dbscSNV1_RF

Benign

0.0080

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

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