Genetic Variant FN1:c.7362+107dupA (chr2-215361861-G-GT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_212482.4(FN1):c.7362+107dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,046,854 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.032 ( 0 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.478

Variant links:

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 links:

ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

ATIC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00215 (315/146802) while in subpopulation EAS AF= 0.0101 (51/5038). AF 95% confidence interval is 0.00791. There are 2 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 315 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4 link	c.7362+107dupA		intron_variant	Intron 45 of 45	ENST00000354785.11	NP_997647.2	P02751-15Q6MZM7Q9UQS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FN1	ENST00000354785.11 link	c.7362+107_7362+108insA		intron_variant	Intron 45 of 45	1	NM_212482.4	ENSP00000346839.4		P02751-15

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

314

AN:

146718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.000644

Gnomad FIN

AF:

0.000846

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000665

Gnomad OTH

AF:

0.00199

GnomAD4 exome

AF:

0.0323

AC:

29080

AN:

900052

Hom.:

Cov.:

AF XY:

0.0319

AC XY:

14114

AN XY:

442604

show subpopulations

Gnomad4 AFR exome

AF:

0.0376

Gnomad4 AMR exome

AF:

0.0321

Gnomad4 ASJ exome

AF:

0.0323

Gnomad4 EAS exome

AF:

0.0310

Gnomad4 SAS exome

AF:

0.0253

Gnomad4 FIN exome

AF:

0.0263

Gnomad4 NFE exome

AF:

0.0330

Gnomad4 OTH exome

AF:

0.0313

GnomAD4 genome

AF:

0.00215

AC:

315

AN:

146802

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

163

AN XY:

71502

show subpopulations

Gnomad4 AFR

AF:

0.00440

Gnomad4 AMR

AF:

0.00184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0101

Gnomad4 SAS

AF:

0.000646

Gnomad4 FIN

AF:

0.000846

Gnomad4 NFE

AF:

0.000665

Gnomad4 OTH

AF:

0.00197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

2-215361861-GTTTTT-GTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over