rs10202709

chr2-215433507-C-T

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.278-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,587,770 control chromosomes in the GnomAD database, including 44,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4020 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40152 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.140

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=-0.83).
• BP6: Variant 2-215433507-C-T is Benign according to our data. Variant chr2-215433507-C-T is described in ClinVar as [Benign]. Clinvar id is 1227596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN1	NM_212482.4	c.278-46G>A		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.278-46G>A		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33545 AN: 151938 Hom.: 4020 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.178 AC: 37656 AN: 211880 Hom.: 4171 AF XY: 0.174 AC XY: 19755 AN XY: 113806

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.000521

Gnomad SAS exome AF: 0.0463

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.226 AC: 324002 AN: 1435714 Hom.: 40152 Cov.: 30 AF XY: 0.219 AC XY: 156189 AN XY: 712354

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.000337

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.221 AC: 33561 AN: 152056 Hom.: 4020 Cov.: 32 AF XY: 0.216 AC XY: 16053 AN XY: 74326

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.201

Alfa AF: 0.222 Hom.: 758

Bravo AF: 0.215

Asia WGS AF: 0.0400 AC: 140 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	-0.83
Cadd	Benign	5.3
Dann	Benign	0.63

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: rs10202709; hg19: chr2-216298230; COSMIC: COSV60566938; COSMIC: COSV60566938;