chrX-108620226-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000328300.11(COL4A5):​c.2510-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,134,069 control chromosomes in the GnomAD database, including 1 homozygotes. There are 121 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., 18 hem., cov: 23)
Exomes 𝑓: 0.00036 ( 1 hom. 103 hem. )

Consequence

COL4A5
ENST00000328300.11 intron

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BS2
High Hemizygotes in GnomAd4 at 18 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL4A5NM_033380.3 linkuse as main transcriptc.2510-33A>G intron_variant ENST00000328300.11 NP_203699.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL4A5ENST00000328300.11 linkuse as main transcriptc.2510-33A>G intron_variant 1 NM_033380.3 ENSP00000331902 P29400-2
COL4A5ENST00000483338.1 linkuse as main transcriptc.1334-33A>G intron_variant 1 ENSP00000495685
COL4A5ENST00000361603.7 linkuse as main transcriptc.2510-33A>G intron_variant 2 ENSP00000354505 P1P29400-1

Frequencies

GnomAD3 genomes
AF:
0.000376
AC:
42
AN:
111661
Hom.:
0
Cov.:
23
AF XY:
0.000503
AC XY:
17
AN XY:
33829
show subpopulations
Gnomad AFR
AF:
0.0000326
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000669
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000639
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000284
AC:
51
AN:
179295
Hom.:
1
AF XY:
0.000273
AC XY:
18
AN XY:
65981
show subpopulations
Gnomad AFR exome
AF:
0.0000784
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000558
Gnomad OTH exome
AF:
0.000451
GnomAD4 exome
AF:
0.000356
AC:
364
AN:
1022356
Hom.:
1
Cov.:
21
AF XY:
0.000335
AC XY:
103
AN XY:
307020
show subpopulations
Gnomad4 AFR exome
AF:
0.0000402
Gnomad4 AMR exome
AF:
0.000285
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000764
Gnomad4 FIN exome
AF:
0.0000248
Gnomad4 NFE exome
AF:
0.000430
Gnomad4 OTH exome
AF:
0.000299
GnomAD4 genome
AF:
0.000385
AC:
43
AN:
111713
Hom.:
0
Cov.:
23
AF XY:
0.000531
AC XY:
18
AN XY:
33891
show subpopulations
Gnomad4 AFR
AF:
0.0000325
Gnomad4 AMR
AF:
0.000668
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000658
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000338
Hom.:
2
Bravo
AF:
0.000408

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

X-linked Alport syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenomic Research Center, Shahid Beheshti University of Medical SciencesApr 27, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
7.8
DANN
Benign
0.68

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.

Other links and lift over

dbSNP: rs104886358; hg19: chrX-107863456; API