rs370313574

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_033380.3(COL4A5):c.31G>A(p.Gly11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 109,008 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G11V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 20)

Consequence

COL4A5
NM_033380.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Alport syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, G2P
X-linked Alport syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)

COL4A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 538 curated pathogenic missense variants (we use a threshold of 10). The gene has 138 curated benign missense variants. Gene score misZ: 2.4995 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to X-linked Alport syndrome, Alport syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.22129813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3 link	c.31G>A	p.Gly11Ser	missense_variant	Exon 1 of 53	ENST00000328300.11	NP_203699.1	P29400-2Q49AM6A7MBN3
COL4A5	NM_000495.5 link	c.31G>A	p.Gly11Ser	missense_variant	Exon 1 of 51		NP_000486.1	P29400-1Q49AM6A7MBN3
COL4A5	XM_047441811.1 link	c.31G>A	p.Gly11Ser	missense_variant	Exon 1 of 42		XP_047297767.1
COL4A5	XM_047441810.1 link	c.-346G>A		5_prime_UTR_variant	Exon 1 of 54		XP_047297766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11 link	c.31G>A	p.Gly11Ser	missense_variant	Exon 1 of 53	1	NM_033380.3	ENSP00000331902.7		P29400-2

Frequencies

GnomAD3 genomes

AF:

0.0000183

AC:

AN:

109008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.00000551

AC:

AN:

181534

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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

Cov.:

GnomAD4 genome

AF:

0.0000183

AC:

AN:

109008

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

31268

show subpopulations

African (AFR)

AF:

0.0000671

AC:

AN:

29798

American (AMR)

AF:

0.00

AC:

AN:

10160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2609

East Asian (EAS)

AF:

0.00

AC:

AN:

3443

South Asian (SAS)

AF:

0.00

AC:

AN:

2432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5617

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52583

Other (OTH)

AF:

0.00

AC:

AN:

1453

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

0.0022

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.11

.;T

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.0

N;N

PhyloP100

1.8

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.56

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.55

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.93

.;P

Vest4

0.44

MVP

0.86

MPC

0.30

ClinPred

0.19

GERP RS

2.9

PromoterAI

-0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.74

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs370313574

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over