rs1250204

Variant names:

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.5622+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,609,764 control chromosomes in the GnomAD database, including 734,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67084 hom., cov: 32)

Exomes 𝑓: 0.96 ( 667137 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.163

Publications

9 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

FN1 links:

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=-0.8).

BP6

Variant 2-215379109-T-C is Benign according to our data. Variant chr2-215379109-T-C is described in ClinVar as Benign. ClinVar VariationId is 1250663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4 link	c.5622+21A>G		intron_variant	Intron 34 of 45	ENST00000354785.11	NP_997647.2	P02751-15Q6MZM7Q9UQS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11 link	c.5622+21A>G		intron_variant	Intron 34 of 45	1	NM_212482.4	ENSP00000346839.4		P02751-15

Frequencies

GnomAD3 genomes

AF:

0.938

AC:

142733

AN:

152114

Hom.:

67039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

0.949

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.972

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.955

Gnomad OTH

AF:

0.940

GnomAD2 exomes

AF:

0.955

AC:

239972

AN:

251240

AF XY:

0.955

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.970

Gnomad ASJ exome

AF:

0.948

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.968

Gnomad NFE exome

AF:

0.957

Gnomad OTH exome

AF:

0.955

GnomAD4 exome

AF:

0.957

AC:

1394229

AN:

1457532

Hom.:

667137

Cov.:

AF XY:

0.956

AC XY:

693581

AN XY:

725460

show subpopulations

African (AFR)

AF:

0.881

AC:

29392

AN:

33364

American (AMR)

AF:

0.966

AC:

43215

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

24716

AN:

26112

East Asian (EAS)

AF:

1.00

AC:

39673

AN:

39682

South Asian (SAS)

AF:

0.939

AC:

80887

AN:

86184

European-Finnish (FIN)

AF:

0.966

AC:

51599

AN:

53416

Middle Eastern (MID)

AF:

0.950

AC:

5469

AN:

5756

European-Non Finnish (NFE)

AF:

0.958

AC:

1061978

AN:

1108074

Other (OTH)

AF:

0.951

AC:

57300

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

3008

6016

9025

12033

15041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21526

43052

64578

86104

107630

<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:

0.938

AC:

142834

AN:

152232

Hom.:

67084

Cov.:

AF XY:

0.940

AC XY:

69951

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.883

AC:

36677

AN:

41524

American (AMR)

AF:

0.962

AC:

14710

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.949

AC:

3296

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5154

AN:

5160

South Asian (SAS)

AF:

0.944

AC:

4553

AN:

4824

European-Finnish (FIN)

AF:

0.972

AC:

10306

AN:

10608

Middle Eastern (MID)

AF:

0.935

AC:

275

AN:

294

European-Non Finnish (NFE)

AF:

0.955

AC:

64996

AN:

68028

Other (OTH)

AF:

0.940

AC:

1988

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

441

882

1323

1764

2205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.940

Hom.:

16964

Bravo

AF:

0.936

Asia WGS

AF:

0.967

AC:

3361

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glomerulopathy with fibronectin deposits 2

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spondylometaphyseal dysplasia - Sutcliffe type

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.55

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over