2-215361919-A-C

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

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]

ATIC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
FN1	NM_212482.4	c.7362+50T>G		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.7362+50T>G		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46073 AN: 151878 Hom.: 7890 Cov.: 32

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

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.: 29 AF XY: 0.347 AC XY: 249674 AN XY: 719838

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.: 32 AF XY: 0.301 AC XY: 22391 AN XY: 74288

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: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	-0.81
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

Other links and lift over

dbSNP: rs13394662; hg19: chr2-216226642; COSMIC: COSV60552112; COSMIC: COSV60552112;