chrX-108206523-A-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_033641.4(COL4A6):​c.604T>C​(p.Leu202Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,207,856 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.000044 ( 0 hom. 15 hem. )

Consequence

COL4A6
NM_033641.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.380

Publications

1 publications found
Variant links:
Genes affected
COL4A6 (HGNC:2208): (collagen type IV alpha 6 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component 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, alpha 5 type IV collagen, so that the gene pair shares a common promoter. Deletions in the alpha 5 gene that extend into the alpha 6 gene result in diffuse leiomyomatosis accompanying the X-linked Alport syndrome caused by the deletion in the alpha 5 gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]
COL4A6 Gene-Disease associations (from GenCC):
  • hearing loss, X-linked 6
    Inheritance: XL Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
  • X-linked nonsyndromic hearing loss
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • premature ovarian failure 1
    Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant X-108206523-A-G is Benign according to our data. Variant chrX-108206523-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 258281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.38 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL4A6NM_033641.4 linkc.604T>C p.Leu202Leu synonymous_variant Exon 9 of 45 ENST00000334504.12 NP_378667.1 Q14031-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL4A6ENST00000334504.12 linkc.604T>C p.Leu202Leu synonymous_variant Exon 9 of 45 5 NM_033641.4 ENSP00000334733.7 Q14031-2

Frequencies

GnomAD3 genomes
AF:
0.0000628
AC:
7
AN:
111530
Hom.:
0
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.0000326
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00229
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000131
AC:
24
AN:
182597
AF XY:
0.000134
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000438
AC:
48
AN:
1096272
Hom.:
0
Cov.:
29
AF XY:
0.0000414
AC XY:
15
AN XY:
362058
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26358
American (AMR)
AF:
0.00
AC:
0
AN:
35133
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19324
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30172
South Asian (SAS)
AF:
0.000739
AC:
40
AN:
54098
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40514
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4122
European-Non Finnish (NFE)
AF:
0.00000119
AC:
1
AN:
840533
Other (OTH)
AF:
0.000152
AC:
7
AN:
46018
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000627
AC:
7
AN:
111584
Hom.:
0
Cov.:
22
AF XY:
0.0000592
AC XY:
2
AN XY:
33808
show subpopulations
African (AFR)
AF:
0.0000325
AC:
1
AN:
30734
American (AMR)
AF:
0.00
AC:
0
AN:
10565
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2627
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3534
South Asian (SAS)
AF:
0.00229
AC:
6
AN:
2615
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6063
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
217
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
53025
Other (OTH)
AF:
0.00
AC:
0
AN:
1517
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000508
Hom.:
0

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Oct 29, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.2
DANN
Benign
0.70
PhyloP100
0.38
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs754963967; hg19: chrX-107449753; API