NM_001846.4:c.3877+28C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001846.4(COL4A2):​c.3877+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,602,492 control chromosomes in the GnomAD database, including 126,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11610 hom., cov: 31)
Exomes 𝑓: 0.39 ( 114995 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.36

Publications

11 publications found
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]
COL4A2 Gene-Disease associations (from GenCC):
  • porencephaly 2
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • COL4A1 or COL4A2-related cerebral small vessel disease
    Inheritance: AD Classification: MODERATE Submitted by: Illumina
  • familial porencephaly
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 13-110501812-C-T is Benign according to our data. Variant chr13-110501812-C-T is described in ClinVar as [Benign]. Clinvar id is 1243167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL4A2NM_001846.4 linkc.3877+28C>T intron_variant Intron 41 of 47 ENST00000360467.7 NP_001837.2 P08572A0A024RDW8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL4A2ENST00000360467.7 linkc.3877+28C>T intron_variant Intron 41 of 47 5 NM_001846.4 ENSP00000353654.5 P08572

Frequencies

GnomAD3 genomes
AF:
0.385
AC:
58381
AN:
151782
Hom.:
11596
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.330
Gnomad AMI
AF:
0.392
Gnomad AMR
AF:
0.476
Gnomad ASJ
AF:
0.418
Gnomad EAS
AF:
0.648
Gnomad SAS
AF:
0.365
Gnomad FIN
AF:
0.341
Gnomad MID
AF:
0.332
Gnomad NFE
AF:
0.384
Gnomad OTH
AF:
0.385
GnomAD2 exomes
AF:
0.418
AC:
101692
AN:
243312
AF XY:
0.409
show subpopulations
Gnomad AFR exome
AF:
0.332
Gnomad AMR exome
AF:
0.577
Gnomad ASJ exome
AF:
0.410
Gnomad EAS exome
AF:
0.641
Gnomad FIN exome
AF:
0.333
Gnomad NFE exome
AF:
0.379
Gnomad OTH exome
AF:
0.386
GnomAD4 exome
AF:
0.392
AC:
569018
AN:
1450594
Hom.:
114995
Cov.:
29
AF XY:
0.391
AC XY:
282098
AN XY:
722078
show subpopulations
African (AFR)
AF:
0.319
AC:
10548
AN:
33042
American (AMR)
AF:
0.561
AC:
24428
AN:
43570
Ashkenazi Jewish (ASJ)
AF:
0.409
AC:
10625
AN:
25982
East Asian (EAS)
AF:
0.688
AC:
27256
AN:
39600
South Asian (SAS)
AF:
0.369
AC:
31451
AN:
85316
European-Finnish (FIN)
AF:
0.333
AC:
17707
AN:
53130
Middle Eastern (MID)
AF:
0.317
AC:
1820
AN:
5734
European-Non Finnish (NFE)
AF:
0.382
AC:
421698
AN:
1104232
Other (OTH)
AF:
0.391
AC:
23485
AN:
59988
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
17814
35629
53443
71258
89072
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
13340
26680
40020
53360
66700
<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:
0.385
AC:
58436
AN:
151898
Hom.:
11610
Cov.:
31
AF XY:
0.386
AC XY:
28686
AN XY:
74234
show subpopulations
African (AFR)
AF:
0.330
AC:
13666
AN:
41438
American (AMR)
AF:
0.477
AC:
7280
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.418
AC:
1452
AN:
3470
East Asian (EAS)
AF:
0.649
AC:
3336
AN:
5142
South Asian (SAS)
AF:
0.366
AC:
1758
AN:
4802
European-Finnish (FIN)
AF:
0.341
AC:
3598
AN:
10560
Middle Eastern (MID)
AF:
0.330
AC:
97
AN:
294
European-Non Finnish (NFE)
AF:
0.384
AC:
26077
AN:
67912
Other (OTH)
AF:
0.388
AC:
816
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1767
3535
5302
7070
8837
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
554
1108
1662
2216
2770
<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:
0.384
Hom.:
2322
Bravo
AF:
0.398
Asia WGS
AF:
0.462
AC:
1605
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 29, 2018
GeneDx
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
-0.91
CADD
Benign
0.44
DANN
Benign
0.48
PhyloP100
-1.4
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs388222; hg19: chr13-111154159; COSMIC: COSV107471777; COSMIC: COSV107471777; API