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GeneBe

2-227027145-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000092.5(COL4A4):c.4081+757A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,286 control chromosomes in the GnomAD database, including 16,827 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 16827 hom., cov: 28)

Consequence

COL4A4
NM_000092.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL4A4NM_000092.5 linkuse as main transcriptc.4081+757A>G intron_variant ENST00000396625.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL4A4ENST00000396625.5 linkuse as main transcriptc.4081+757A>G intron_variant 5 NM_000092.5 P1

Frequencies

GnomAD3 genomes
AF:
0.469
AC:
70856
AN:
151168
Hom.:
16793
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.534
Gnomad AMI
AF:
0.401
Gnomad AMR
AF:
0.470
Gnomad ASJ
AF:
0.496
Gnomad EAS
AF:
0.386
Gnomad SAS
AF:
0.546
Gnomad FIN
AF:
0.492
Gnomad MID
AF:
0.414
Gnomad NFE
AF:
0.427
Gnomad OTH
AF:
0.435
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.469
AC:
70935
AN:
151286
Hom.:
16827
Cov.:
28
AF XY:
0.470
AC XY:
34698
AN XY:
73866
show subpopulations
Gnomad4 AFR
AF:
0.534
Gnomad4 AMR
AF:
0.471
Gnomad4 ASJ
AF:
0.496
Gnomad4 EAS
AF:
0.386
Gnomad4 SAS
AF:
0.545
Gnomad4 FIN
AF:
0.492
Gnomad4 NFE
AF:
0.427
Gnomad4 OTH
AF:
0.430
Alfa
AF:
0.339
Hom.:
992
Bravo
AF:
0.471
Asia WGS
AF:
0.476
AC:
1659
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
Cadd
Benign
5.1
Dann
Benign
0.49

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.

Other links and lift over

dbSNP: rs1949807; hg19: chr2-227891861; API