rs2272945

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033380.3(COL4A5):c.1095G>C(p.Gly365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,205,928 control chromosomes in the GnomAD database, including 2,808 homozygotes. There are 8,319 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1347 hom., 3194 hem., cov: 22)

Exomes 𝑓: 0.016 ( 1461 hom. 5125 hem. )

Consequence

COL4A5
NM_033380.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.895

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-108586677-G-C is Benign according to our data. Variant chrX-108586677-G-C is described in ClinVar as [Benign]. Clinvar id is 24365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108586677-G-C is described in Lovd as [Benign]. Variant chrX-108586677-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.895 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3 linkuse as main transcript	c.1095G>C	p.Gly365=	synonymous_variant	19/53	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.1095G>C	p.Gly365=	synonymous_variant	19/53	1	NM_033380.3	ENSP00000331902		P29400-2
COL4A5	ENST00000483338.1 linkuse as main transcript	c.-82G>C		5_prime_UTR_variant	3/20	1		ENSP00000495685
COL4A5	ENST00000361603.7 linkuse as main transcript	c.1095G>C	p.Gly365=	synonymous_variant	19/51	2		ENSP00000354505	P1	P29400-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

11721

AN:

110336

Hom.:

1347

Cov.:

AF XY:

0.0973

AC XY:

3179

AN XY:

32672

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0563

Gnomad ASJ

AF:

0.00304

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.0894

GnomAD3 exomes

AF:

0.0458

AC:

8396

AN:

183258

Hom.:

733

AF XY:

0.0344

AC XY:

2332

AN XY:

67748

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.0437

Gnomad ASJ exome

AF:

0.00374

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000843

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0162

AC:

17771

AN:

1095540

Hom.:

1461

Cov.:

AF XY:

0.0142

AC XY:

5125

AN XY:

361180

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.0470

Gnomad4 ASJ exome

AF:

0.00362

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.000605

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.106

AC:

11733

AN:

110388

Hom.:

1347

Cov.:

AF XY:

0.0976

AC XY:

3194

AN XY:

32734

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.0560

Gnomad4 ASJ

AF:

0.00304

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0208

Gnomad4 FIN

AF:

0.000168

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.0883

Alfa

AF:

0.0156

Hom.:

102

Bravo

AF:

0.123

EpiCase

AF:

0.000928

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	p.Gly365Gly in exon 19 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 40.08% (402/1003) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs2272945). -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

X-linked Alport syndrome

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 26, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.2

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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