Variant rs2272205 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_000092.5(COL4A4):c.2969-50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 1,593,442 control chromosomes in the GnomAD database, including 7,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 539 hom., cov: 32)

Exomes 𝑓: 0.094 ( 6669 hom. )

Consequence

COL4A4
NM_000092.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.894

Variant links:

Genes affected

COL4A4 (HGNC:2206): (collagen type IV alpha 4 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. 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. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]

COL4A4 links:

COL4A4 (HGNC:):

COL4A4 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=-0.9).

BP6

Variant 2-227051208-T-C is Benign according to our data. Variant chr2-227051208-T-C is described in ClinVar as [Benign]. Clinvar id is 682773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-227051208-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A4	NM_000092.5 linkuse as main transcript	c.2969-50A>G		intron_variant		ENST00000396625.5	NP_000083.3	P53420

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A4	ENST00000396625.5 linkuse as main transcript	c.2969-50A>G		intron_variant		5	NM_000092.5	ENSP00000379866.3		P53420

Frequencies

GnomAD3 genomes

AF:

0.0798

AC:

12127

AN:

152062

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0732

Gnomad ASJ

AF:

0.0851

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0621

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0917

Gnomad OTH

AF:

0.0880

GnomAD3 exomes

AF:

0.0906

AC:

22490

AN:

248274

Hom.:

1163

AF XY:

0.0944

AC XY:

12730

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.0515

Gnomad ASJ exome

AF:

0.0878

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.0636

Gnomad NFE exome

AF:

0.0914

Gnomad OTH exome

AF:

0.0950

GnomAD4 exome

AF:

0.0936

AC:

134950

AN:

1441262

Hom.:

6669

Cov.:

AF XY:

0.0950

AC XY:

68267

AN XY:

718308

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.0530

Gnomad4 ASJ exome

AF:

0.0841

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0651

Gnomad4 NFE exome

AF:

0.0926

Gnomad4 OTH exome

AF:

0.0954

GnomAD4 genome

AF:

0.0798

AC:

12140

AN:

152180

Hom.:

539

Cov.:

AF XY:

0.0796

AC XY:

5922

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0482

Gnomad4 AMR

AF:

0.0730

Gnomad4 ASJ

AF:

0.0851

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.0621

Gnomad4 NFE

AF:

0.0917

Gnomad4 OTH

AF:

0.0932

Alfa

AF:

0.0906

Hom.:

1098

Bravo

AF:

0.0773

Asia WGS

AF:

0.154

AC:

533

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive Alport syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.73

DANN

Benign

0.50

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