rs9559826

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001846.4(COL4A2):​c.3634+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 735,544 control chromosomes in the GnomAD database, including 3,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 770 hom., cov: 32)
Exomes 𝑓: 0.097 ( 2969 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.84
Variant links:
Genes affected
COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. 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. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 13-110493432-C-T is Benign according to our data. Variant chr13-110493432-C-T is described in ClinVar as [Benign]. Clinvar id is 1223587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL4A2NM_001846.4 linkuse as main transcriptc.3634+150C>T intron_variant ENST00000360467.7 NP_001837.2 P08572A0A024RDW8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL4A2ENST00000360467.7 linkuse as main transcriptc.3634+150C>T intron_variant 5 NM_001846.4 ENSP00000353654.5 P08572
COL4A2ENST00000650225.1 linkuse as main transcriptn.1289+150C>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.100
AC:
15226
AN:
152116
Hom.:
768
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0969
Gnomad AMI
AF:
0.189
Gnomad AMR
AF:
0.0934
Gnomad ASJ
AF:
0.0616
Gnomad EAS
AF:
0.168
Gnomad SAS
AF:
0.0742
Gnomad FIN
AF:
0.0723
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.106
Gnomad OTH
AF:
0.0847
GnomAD4 exome
AF:
0.0967
AC:
56434
AN:
583310
Hom.:
2969
AF XY:
0.0956
AC XY:
29262
AN XY:
306030
show subpopulations
Gnomad4 AFR exome
AF:
0.0925
Gnomad4 AMR exome
AF:
0.106
Gnomad4 ASJ exome
AF:
0.0561
Gnomad4 EAS exome
AF:
0.128
Gnomad4 SAS exome
AF:
0.0698
Gnomad4 FIN exome
AF:
0.0789
Gnomad4 NFE exome
AF:
0.101
Gnomad4 OTH exome
AF:
0.0945
GnomAD4 genome
AF:
0.100
AC:
15244
AN:
152234
Hom.:
770
Cov.:
32
AF XY:
0.0996
AC XY:
7418
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0970
Gnomad4 AMR
AF:
0.0932
Gnomad4 ASJ
AF:
0.0616
Gnomad4 EAS
AF:
0.168
Gnomad4 SAS
AF:
0.0743
Gnomad4 FIN
AF:
0.0723
Gnomad4 NFE
AF:
0.106
Gnomad4 OTH
AF:
0.0852
Alfa
AF:
0.104
Hom.:
326
Bravo
AF:
0.103
Asia WGS
AF:
0.107
AC:
372
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.1
DANN
Benign
0.77

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: rs9559826; hg19: chr13-111145779; API