chr2-215397898-A-C

Position:

• chr2-215397898-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_212482.4(FN1):​c.3349-50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,521,204 control chromosomes in the GnomAD database, including 262,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28696 hom., cov: 32)
  • Exomes 𝑓: 0.58 (234300 hom.)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.418

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-215397898-A-C is Benign according to our data. Variant chr2-215397898-A-C is described in ClinVar as [Benign]. Clinvar id is 1227605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN1	NM_212482.4	c.3349-50T>G		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.3349-50T>G		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92648 AN: 151964 Hom.: 28695 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.608 AC: 151758 AN: 249656 Hom.: 47571 AF XY: 0.596 AC XY: 80457 AN XY: 134916

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.689

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.931

Gnomad SAS exome AF: 0.469

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.580 AC: 794673 AN: 1369122 Hom.: 234300 Cov.: 21 AF XY: 0.576 AC XY: 395013 AN XY: 686348

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.946

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.609 AC: 92678 AN: 152082 Hom.: 28696 Cov.: 32 AF XY: 0.613 AC XY: 45536 AN XY: 74342

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.610

Alfa AF: 0.539 Hom.: 3510

Bravo AF: 0.622

Asia WGS AF: 0.676 AC: 2355 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	0.83
DANN	Benign	0.62

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: rs6725958; hg19: chr2-216262621;