rs2304573

Positions:

• chr2-215378927-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.5622+203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,160 control chromosomes in the GnomAD database, including 6,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6763 hom., cov: 33)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.400

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=-0.86).
• BP6: Variant 2-215378927-A-G is Benign according to our data. Variant chr2-215378927-A-G is described in ClinVar as [Benign]. Clinvar id is 1239974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FN1	NM_212482.4	c.5622+203T>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.5622+203T>C		intron_variant		1	NM_212482.4	ENSP00000346839	P1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42279 AN: 152042 Hom.: 6763 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42304 AN: 152160 Hom.: 6763 Cov.: 33 AF XY: 0.285 AC XY: 21194 AN XY: 74392

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.295

Alfa AF: 0.263 Hom.: 9608

Bravo AF: 0.291

Asia WGS AF: 0.499 AC: 1737 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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.67

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: rs2304573; hg19: chr2-216243650;