2-215397898-A-C

Variant summary

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

The NM_212482.4(FN1):​c.3349-50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,521,204 control chromosomes in the GnomAD database, including 262,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28696 hom., cov: 32)
Exomes 𝑓: 0.58 ( 234300 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.418

Publications

11 publications found
Variant links:
Genes affected
FN1 (HGNC:3778): (fibronectin 1) This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. The encoded preproprotein is proteolytically processed to generate the mature protein. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. The full-length nature of some variants has not been determined. [provided by RefSeq, Jan 2016]
FN1 Gene-Disease associations (from GenCC):
  • spondylometaphyseal dysplasia, 'corner fracture' type
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics, ClinGen
  • glomerulopathy with fibronectin deposits 2
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
  • fibronectin glomerulopathy
    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=-0.82).
BP6
Variant 2-215397898-A-C is Benign according to our data. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215397898-A-C is described in CliVar as Benign. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FN1NM_212482.4 linkc.3349-50T>G intron_variant Intron 21 of 45 ENST00000354785.11 NP_997647.2 P02751-15Q6MZM7Q9UQS6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FN1ENST00000354785.11 linkc.3349-50T>G intron_variant Intron 21 of 45 1 NM_212482.4 ENSP00000346839.4 P02751-15

Frequencies

GnomAD3 genomes
AF:
0.610
AC:
92648
AN:
151964
Hom.:
28695
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.651
Gnomad AMI
AF:
0.591
Gnomad AMR
AF:
0.658
Gnomad ASJ
AF:
0.606
Gnomad EAS
AF:
0.932
Gnomad SAS
AF:
0.476
Gnomad FIN
AF:
0.608
Gnomad MID
AF:
0.627
Gnomad NFE
AF:
0.559
Gnomad OTH
AF:
0.606
GnomAD2 exomes
AF:
0.608
AC:
151758
AN:
249656
AF XY:
0.596
show subpopulations
Gnomad AFR exome
AF:
0.656
Gnomad AMR exome
AF:
0.689
Gnomad ASJ exome
AF:
0.602
Gnomad EAS exome
AF:
0.931
Gnomad FIN exome
AF:
0.600
Gnomad NFE exome
AF:
0.564
Gnomad OTH exome
AF:
0.598
GnomAD4 exome
AF:
0.580
AC:
794673
AN:
1369122
Hom.:
234300
Cov.:
21
AF XY:
0.576
AC XY:
395013
AN XY:
686348
show subpopulations
African (AFR)
AF:
0.647
AC:
20429
AN:
31562
American (AMR)
AF:
0.687
AC:
30577
AN:
44512
Ashkenazi Jewish (ASJ)
AF:
0.596
AC:
15238
AN:
25562
East Asian (EAS)
AF:
0.946
AC:
37137
AN:
39248
South Asian (SAS)
AF:
0.473
AC:
39898
AN:
84342
European-Finnish (FIN)
AF:
0.598
AC:
31779
AN:
53174
Middle Eastern (MID)
AF:
0.618
AC:
3434
AN:
5558
European-Non Finnish (NFE)
AF:
0.567
AC:
582266
AN:
1027812
Other (OTH)
AF:
0.591
AC:
33915
AN:
57352
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
16621
33242
49862
66483
83104
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
15934
31868
47802
63736
79670
<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:
0.609
AC:
92678
AN:
152082
Hom.:
28696
Cov.:
32
AF XY:
0.613
AC XY:
45536
AN XY:
74342
show subpopulations
African (AFR)
AF:
0.650
AC:
26960
AN:
41472
American (AMR)
AF:
0.657
AC:
10042
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.606
AC:
2100
AN:
3466
East Asian (EAS)
AF:
0.932
AC:
4820
AN:
5172
South Asian (SAS)
AF:
0.476
AC:
2294
AN:
4822
European-Finnish (FIN)
AF:
0.608
AC:
6430
AN:
10578
Middle Eastern (MID)
AF:
0.633
AC:
186
AN:
294
European-Non Finnish (NFE)
AF:
0.559
AC:
38021
AN:
67980
Other (OTH)
AF:
0.610
AC:
1287
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1883
3766
5650
7533
9416
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
758
1516
2274
3032
3790
<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:
0.539
Hom.:
3510
Bravo
AF:
0.622
Asia WGS
AF:
0.676
AC:
2355
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
Aug 20, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.83
DANN
Benign
0.62
PhyloP100
-0.42
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs6725958; hg19: chr2-216262621; API