2-215375861-T-G

Position:

• chr2-215375861-T-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.5888-143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 693,018 control chromosomes in the GnomAD database, including 38,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8480 hom., cov: 33)
  • Exomes 𝑓: 0.30 (29590 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.928

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=-0.76).
• BP6: Variant 2-215375861-T-G is Benign according to our data. Variant chr2-215375861-T-G is described in ClinVar as [Benign]. Clinvar id is 1248775.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	UniProt
FN1	NM_212482.4	c.5888-143A>C		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.5888-143A>C		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47714 AN: 151972 Hom.: 8473 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.298 AC: 160994 AN: 540928 Hom.: 29590 AF XY: 0.292 AC XY: 85440 AN XY: 292814

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.817

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.314 AC: 47758 AN: 152090 Hom.: 8480 Cov.: 33 AF XY: 0.319 AC XY: 23748 AN XY: 74350

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.322

Alfa AF: 0.255 Hom.: 6985

Bravo AF: 0.332

Asia WGS AF: 0.508 AC: 1769 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	-0.76
CADD	Benign	8.8
DANN	Benign	0.80

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: rs6707530; hg19: chr2-216240584;