rs1250248

Positions:

• chr2-215422370-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_212482.4(FN1):​c.1394-127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 948,840 control chromosomes in the GnomAD database, including 268,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45722 hom., cov: 33)
  • Exomes 𝑓: 0.74 (222401 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.322

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-215422370-A-G is Benign according to our data. Variant chr2-215422370-A-G is described in ClinVar as [Benign]. Clinvar id is 1286397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FN1	NM_212482.4	c.1394-127T>C		intron_variant		ENST00000354785.11	NP_997647.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11	c.1394-127T>C		intron_variant		1	NM_212482.4	ENSP00000346839	P1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117534 AN: 152008 Hom.: 45698 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.767

GnomAD4 exome AF: 0.744 AC: 592929 AN: 796712 Hom.: 222401 AF XY: 0.737 AC XY: 310114 AN XY: 420810

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.802

Gnomad4 EAS exome AF: 0.938

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.759

GnomAD4 genome AF: 0.773 AC: 117608 AN: 152128 Hom.: 45722 Cov.: 33 AF XY: 0.777 AC XY: 57766 AN XY: 74382

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.769

Alfa AF: 0.739 Hom.: 19217

Bravo AF: 0.778

Asia WGS AF: 0.719 AC: 2504 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs1250248; hg19: chr2-216287093;