rs3796123

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1819+7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,612,308 control chromosomes in the GnomAD database, including 70,263 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7473 hom., cov: 32)

Exomes 𝑓: 0.26 ( 62790 hom. )

Consequence

FN1
NM_212482.4 splice_region, intron

Scores

Splicing: ADA: 0.0005096

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.99

Publications

15 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=-0.7).

BP6

Variant 2-215419235-T-A is Benign according to our data. Variant chr2-215419235-T-A is described in ClinVar as [Benign]. Clinvar id is 1165946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4 link	c.1819+7A>T		splice_region_variant, intron_variant	Intron 12 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.1819+7A>T		splice_region_variant, intron_variant	Intron 12 of 45	1	NM_212482.4	ENSP00000346839.4		P02751-15

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42694

AN:

151986

Hom.:

7476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.924

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.336

AC:

84332

AN:

251100

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.521

Gnomad ASJ exome

AF:

0.359

Gnomad EAS exome

AF:

0.924

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.263

AC:

383513

AN:

1460204

Hom.:

62790

Cov.:

AF XY:

0.262

AC XY:

190272

AN XY:

726526

show subpopulations

African (AFR)

AF:

0.223

AC:

7470

AN:

33444

American (AMR)

AF:

0.511

AC:

22829

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

9283

AN:

26114

East Asian (EAS)

AF:

0.936

AC:

37141

AN:

39688

South Asian (SAS)

AF:

0.253

AC:

21817

AN:

86214

European-Finnish (FIN)

AF:

0.275

AC:

14688

AN:

53404

Middle Eastern (MID)

AF:

0.322

AC:

1854

AN:

5766

European-Non Finnish (NFE)

AF:

0.226

AC:

250762

AN:

1110544

Other (OTH)

AF:

0.293

AC:

17669

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

12112

24223

36335

48446

60558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.281

AC:

42709

AN:

152104

Hom.:

7473

Cov.:

AF XY:

0.290

AC XY:

21587

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.226

AC:

9361

AN:

41472

American (AMR)

AF:

0.420

AC:

6413

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1252

AN:

3470

East Asian (EAS)

AF:

0.923

AC:

4768

AN:

5166

South Asian (SAS)

AF:

0.268

AC:

1289

AN:

4818

European-Finnish (FIN)

AF:

0.291

AC:

3073

AN:

10578

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15671

AN:

68004

Other (OTH)

AF:

0.303

AC:

639

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1425

2851

4276

5702

7127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.256

Hom.:

1796

Bravo

AF:

0.296

Asia WGS

AF:

0.552

AC:

1919

AN:

3478

EpiCase

AF:

0.248

EpiControl

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

-0.70

CADD

Benign

9.5

(source)

DANN

Benign

0.62

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00051

dbscSNV1_RF

Benign

0.0060

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.

rs3796123

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