rs1525351

chr2-215398643-G-Achr2-215398643-G-Cchr2-215398643-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_212482.4(FN1):c.3348+614C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,052 control chromosomes in the GnomAD database, including 26,198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26198 hom., cov: 33)
• Consequence: FN1 NM_212482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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.3348+614C>T		intron_variant		ENST00000354785.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN1	ENST00000354785.11	c.3348+614C>T		intron_variant		1	NM_212482.4	P1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88489 AN: 151932 Hom.: 26192 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.582 AC: 88528 AN: 152052 Hom.: 26198 Cov.: 33 AF XY: 0.586 AC XY: 43563 AN XY: 74326

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.588

Alfa AF: 0.562 Hom.: 27432

Bravo AF: 0.591

Asia WGS AF: 0.667 AC: 2319 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	0.61

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: rs1525351; hg19: chr2-216263366;