Variant chrX-108597204-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033380.3(COL4A5):c.1587+136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 740,527 control chromosomes in the GnomAD database, including 17,928 homozygotes. There are 53,617 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2071 hom., 6494 hem., cov: 22)

Exomes 𝑓: 0.24 ( 15857 hom. 47123 hem. )

Consequence

COL4A5
NM_033380.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.686

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-108597204-A-G is Benign according to our data. Variant chrX-108597204-A-G is described in ClinVar as [Benign]. Clinvar id is 1177027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108597204-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3 linkuse as main transcript	c.1587+136A>G		intron_variant		ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11 linkuse as main transcript	c.1587+136A>G	intron_variant	1	NM_033380.3	ENSP00000331902		P29400-2
COL4A5	ENST00000483338.1 linkuse as main transcript	c.411+136A>G	intron_variant	1		ENSP00000495685
COL4A5	ENST00000361603.7 linkuse as main transcript	c.1587+136A>G	intron_variant	2		ENSP00000354505	P1	P29400-1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

21478

AN:

110359

Hom.:

2071

Cov.:

AF XY:

0.198

AC XY:

6479

AN XY:

32681

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.186

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.241

AC:

152046

AN:

630114

Hom.:

15857

AF XY:

0.273

AC XY:

47123

AN XY:

172856

show subpopulations

Gnomad4 AFR exome

AF:

0.0629

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.195

AC:

21490

AN:

110413

Hom.:

2071

Cov.:

AF XY:

0.198

AC XY:

6494

AN XY:

32745

show subpopulations

Gnomad4 AFR

AF:

0.0641

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.572

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.171

Hom.:

1287

Bravo

AF:

0.215

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

X-linked Alport syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

DANN

Benign

0.65

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

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