rs1250215

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_212482.4(FN1):c.4253-15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,591,364 control chromosomes in the GnomAD database, including 295,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 21816 hom., cov: 32)

Exomes 𝑓: 0.61 ( 273392 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0390

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 links:

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=-0.83).

BP6

Variant 2-215388316-G-C is Benign according to our data. Variant chr2-215388316-G-C is described in ClinVar as [Benign]. Clinvar id is 1284045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215388316-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4 link	c.4253-15C>G		intron_variant	Intron 26 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.4253-15C>G		intron_variant	Intron 26 of 45	1	NM_212482.4	ENSP00000346839.4		P02751-15

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77897

AN:

151976

Hom.:

21813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.608

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.483

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.497

GnomAD3 exomes

AF:

0.546

AC:

136948

AN:

250956

Hom.:

39550

AF XY:

0.555

AC XY:

75306

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.557

Gnomad FIN exome

AF:

0.685

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.558

GnomAD4 exome

AF:

0.608

AC:

875270

AN:

1439270

Hom.:

273392

Cov.:

AF XY:

0.607

AC XY:

435728

AN XY:

717548

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.558

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.644

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.512

AC:

77927

AN:

152094

Hom.:

21816

Cov.:

AF XY:

0.511

AC XY:

37993

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.483

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.686

Gnomad4 NFE

AF:

0.640

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.502

Hom.:

2879

Bravo

AF:

0.486

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, 2025

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

-0.83

CADD

Benign

7.9

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over