Variant rs3752896 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.4091-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,611,764 control chromosomes in the GnomAD database, including 153,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 13996 hom., cov: 32)

Exomes 𝑓: 0.43 ( 139705 hom. )

Consequence

COL4A4
NM_000092.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.98

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:

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=-0.87).

BP6

Variant 2-227022209-C-T is Benign according to our data. Variant chr2-227022209-C-T is described in ClinVar as [Benign]. Clinvar id is 1184793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-227022209-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 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.4091-36G>A		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.4091-36G>A		intron_variant		5	NM_000092.5	ENSP00000379866.3		P53420

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64842

AN:

151828

Hom.:

13971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.404

GnomAD3 exomes

AF:

0.460

AC:

113799

AN:

247294

Hom.:

26688

AF XY:

0.460

AC XY:

61867

AN XY:

134392

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.507

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.558

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.434

AC:

634123

AN:

1459818

Hom.:

139705

Cov.:

AF XY:

0.437

AC XY:

317267

AN XY:

726332

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.521

Gnomad4 ASJ exome

AF:

0.515

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.495

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.427

AC:

64910

AN:

151946

Hom.:

13996

Cov.:

AF XY:

0.430

AC XY:

31956

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.396

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.391

Gnomad4 SAS

AF:

0.550

Gnomad4 FIN

AF:

0.490

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.440

Hom.:

2742

Bravo

AF:

0.424

Asia WGS

AF:

0.469

AC:

1633

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 65. Only high quality variants are reported. -

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

-0.87

CADD

Benign

0.074

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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