Variant rs1250204 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).

BP6

Variant 2-215379109-T-C is Benign according to our data. Variant chr2-215379109-T-C is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
FN1	NM_212482.4 linkuse as main transcript	c.5622+21A>G		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11 linkuse as main transcript	c.5622+21A>G		intron_variant		1	NM_212482.4	P1	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

GnomAD3 exomes

AF:

0.955

AC:

239972

AN:

251240

Hom.:

114700

AF XY:

0.955

AC XY:

129706

AN XY:

135778

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 SAS exome

AF:

0.938

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

Gnomad4 AFR exome

AF:

0.881

Gnomad4 AMR exome

AF:

0.966

Gnomad4 ASJ exome

AF:

0.947

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.939

Gnomad4 FIN exome

AF:

0.966

Gnomad4 NFE exome

AF:

0.958

Gnomad4 OTH exome

AF:

0.951

GnomAD4 genome

AF:

0.938

AC:

142834

AN:

152232

Hom.:

67084

Cov.:

AF XY:

0.940

AC XY:

69951

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.883

Gnomad4 AMR

AF:

0.962

Gnomad4 ASJ

AF:

0.949

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.944

Gnomad4 FIN

AF:

0.972

Gnomad4 NFE

AF:

0.955

Gnomad4 OTH

AF:

0.940

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.80

CADD

Benign

1.3

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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