rs1525351

Variant names:

• chr2-215398643-G-A
• rs1525351
• NM_212482.4:c.3348+614C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-215398643-G-A
• chr2-215398643-G-C
• chr2-215398643-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

FN1 Gene-Disease associations (from GenCC):

• spondylometaphyseal dysplasia, 'corner fracture' type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics, ClinGen
• glomerulopathy with fibronectin deposits 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• fibronectin glomerulopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FN1	NM_212482.4	c.3348+614C>T		intron_variant	Intron 21 of 45	ENST00000354785.11	NP_997647.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11	c.3348+614C>T		intron_variant	Intron 21 of 45	1	NM_212482.4	ENSP00000346839.4

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

African (AFR) AF: 0.559 AC: 23177 AN: 41470

American (AMR) AF: 0.645 AC: 9862 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2096 AN: 3466

East Asian (EAS) AF: 0.932 AC: 4830 AN: 5182

South Asian (SAS) AF: 0.459 AC: 2209 AN: 4808

European-Finnish (FIN) AF: 0.608 AC: 6430 AN: 10572

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37961 AN: 67954

Other (OTH) AF: 0.588 AC: 1241 AN: 2110

Alfa AF: 0.567 Hom.: 47595

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
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1525351; hg19: chr2-216263366;