rs144586397

Positions:

chrX-108581000-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033380.3(COL4A5):c.909T>C(p.Asp303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,207,337 control chromosomes in the GnomAD database, including 17 homozygotes. There are 255 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., 41 hem., cov: 22)

Exomes 𝑓: 0.00080 ( 14 hom. 214 hem. )

Consequence

COL4A5
NM_033380.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.15

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]

COL4A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-108581000-T-C is Benign according to our data. Variant chrX-108581000-T-C is described in ClinVar as [Benign]. Clinvar id is 504907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108581000-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00125 (139/111536) while in subpopulation AMR AF= 0.0129 (134/10426). AF 95% confidence interval is 0.0111. There are 3 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3 linkuse as main transcript	c.909T>C	p.Asp303=	synonymous_variant	16/53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11 linkuse as main transcript	c.909T>C	p.Asp303=	synonymous_variant	16/53	1	NM_033380.3	ENSP00000331902		P29400-2
COL4A5	ENST00000361603.7 linkuse as main transcript	c.909T>C	p.Asp303=	synonymous_variant	16/51	2		ENSP00000354505	P1	P29400-1

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

139

AN:

111485

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

33679

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

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:

0.00

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.00379

AC:

694

AN:

183338

Hom.:

AF XY:

0.00251

AC XY:

170

AN XY:

67818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0250

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:

0.0000122

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.000801

AC:

878

AN:

1095801

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

214

AN XY:

361365

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.000522

GnomAD4 genome

AF:

0.00125

AC:

139

AN:

111536

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

33740

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000660

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00229

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 19, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

p.Asp303Asp in exon 16 of COL4A5: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 2.64% (245/9283) o f Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs144586397). -

X-linked Alport syndrome

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Dec 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.9

DANN

Benign

0.61

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.

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