Variant 2-215361919-A-C 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.7362+50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,598,568 control chromosomes in the GnomAD database, including 104,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7895 hom., cov: 32)

Exomes 𝑓: 0.35 ( 96919 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0170

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-215361919-A-C is Benign according to our data. Variant chr2-215361919-A-C is described in ClinVar as [Benign]. Clinvar id is 1222395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 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.7362+50T>G		intron_variant		ENST00000354785.11	NP_997647.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11 linkuse as main transcript	c.7362+50T>G		intron_variant		1	NM_212482.4	ENSP00000346839	P1	P02751-15

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46073

AN:

151878

Hom.:

7890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.452

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.294

AC:

72132

AN:

245560

Hom.:

12683

AF XY:

0.294

AC XY:

38893

AN XY:

132476

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.000992

Gnomad SAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.386

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.352

AC:

509809

AN:

1446572

Hom.:

96919

Cov.:

AF XY:

0.347

AC XY:

249674

AN XY:

719838

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.00177

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.324

GnomAD4 genome

AF:

0.303

AC:

46095

AN:

151996

Hom.:

7895

Cov.:

AF XY:

0.301

AC XY:

22391

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.363

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.355

Hom.:

1904

Bravo

AF:

0.286

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

DANN

Benign

0.56

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