chrX-108440134-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting

The NM_033380.3(COL4A5):​c.9G>A​(p.Leu3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,943 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

COL4A5
NM_033380.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86
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=-0.48).
BP6
Variant X-108440134-G-A is Benign according to our data. Variant chrX-108440134-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1096343.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.86 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL4A5NM_033380.3 linkuse as main transcriptc.9G>A p.Leu3= synonymous_variant 1/53 ENST00000328300.11 NP_203699.1
COL4A5NM_000495.5 linkuse as main transcriptc.9G>A p.Leu3= synonymous_variant 1/51 NP_000486.1
COL4A5XM_047441811.1 linkuse as main transcriptc.9G>A p.Leu3= synonymous_variant 1/42 XP_047297767.1
COL4A5XM_047441810.1 linkuse as main transcriptc.-368G>A 5_prime_UTR_variant 1/54 XP_047297766.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL4A5ENST00000328300.11 linkuse as main transcriptc.9G>A p.Leu3= synonymous_variant 1/531 NM_033380.3 ENSP00000331902 P29400-2

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD3 exomes
AF:
0.00000552
AC:
1
AN:
181114
Hom.:
0
AF XY:
0.0000152
AC XY:
1
AN XY:
65702
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
3
AN:
1095943
Hom.:
0
Cov.:
29
AF XY:
0.00000553
AC XY:
2
AN XY:
361371
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000103
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
21

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 31, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
12
DANN
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs763257714; hg19: chrX-107683364; API