rs3796123

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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=-0.7).

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. Variant chr2-215419235-T-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
FN1	NM_212482.4 linkuse as main transcript	c.1819+7A>T		splice_region_variant, intron_variant		ENST00000354785.11	NP_997647.2	P02751-15Q6MZM7Q9UQS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11 linkuse as main transcript	c.1819+7A>T		splice_region_variant, intron_variant		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

GnomAD3 exomes

AF:

0.336

AC:

84332

AN:

251100

Hom.:

19051

AF XY:

0.323

AC XY:

43774

AN XY:

135710

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 SAS exome

AF:

0.246

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

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.936

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.281

AC:

42709

AN:

152104

Hom.:

7473

Cov.:

AF XY:

0.290

AC XY:

21587

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.420

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.923

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.303

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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

-0.70

CADD

Benign

9.5

DANN

Benign

0.62

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

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