rs11651

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_212482.4(FN1):c.7161T>C(p.Tyr2387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,573,182 control chromosomes in the GnomAD database, including 85,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6170 hom., cov: 31)

Exomes 𝑓: 0.33 ( 79067 hom. )

Consequence

FN1
NM_212482.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.46

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:

ATIC (HGNC:):

ATIC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-215364969-A-G is Benign according to our data. Variant chr2-215364969-A-G is described in ClinVar as [Benign]. Clinvar id is 1169959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215364969-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN1	NM_212482.4 linkuse as main transcript	c.7161T>C	p.Tyr2387=	synonymous_variant	44/46	ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11 linkuse as main transcript	c.7161T>C	p.Tyr2387=	synonymous_variant	44/46	1	NM_212482.4	P1	P02751-15

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39727

AN:

151892

Hom.:

6160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0943

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.322

AC:

63322

AN:

196418

Hom.:

11035

AF XY:

0.335

AC XY:

34885

AN XY:

104080

show subpopulations

Gnomad AFR exome

AF:

0.0876

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.327

AC:

465312

AN:

1421172

Hom.:

79067

Cov.:

AF XY:

0.333

AC XY:

234233

AN XY:

703216

show subpopulations

Gnomad4 AFR exome

AF:

0.0797

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.489

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.262

AC:

39757

AN:

152010

Hom.:

6170

Cov.:

AF XY:

0.262

AC XY:

19453

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0945

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.352

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.315

Hom.:

10007

Bravo

AF:

0.255

Asia WGS

AF:

0.400

AC:

1391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Glomerulopathy with fibronectin deposits 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Spondylometaphyseal dysplasia - Sutcliffe type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

0.38

Dann

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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