Genetic Variant FN1:c.7362+105_7362+107delAAA (chr2-215361861-GTTT-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_212482.4(FN1):c.7362+105_7362+107delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 985,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

FN1
NM_212482.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.820

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

AICA-ribosiduria
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ATIC links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212482.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FN1	NM_212482.4	MANE Select	c.7362+105_7362+107delAAA	intron	N/A	NP_997647.2	P02751-15
FN1	NM_001306129.2		c.7269+105_7269+107delAAA	intron	N/A	NP_001293058.2	P02751-7
FN1	NM_001365517.2		c.7092+105_7092+107delAAA	intron	N/A	NP_001352446.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FN1	ENST00000354785.11	TSL:1 MANE Select	c.7362+105_7362+107delAAA	intron	N/A	ENSP00000346839.4	P02751-15
FN1	ENST00000323926.10	TSL:1	c.7269+105_7269+107delAAA	intron	N/A	ENSP00000323534.6	P02751-7
FN1	ENST00000336916.8	TSL:1	c.6996+105_6996+107delAAA	intron	N/A	ENSP00000338200.4	P02751-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000101

AC:

AN:

985832

Hom.:

AF XY:

0.00

AC XY:

AN XY:

487014

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22020

American (AMR)

AF:

0.00

AC:

AN:

22252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17568

East Asian (EAS)

AF:

0.00

AC:

AN:

25976

South Asian (SAS)

AF:

0.00

AC:

AN:

54784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2856

European-Non Finnish (NFE)

AF:

0.00000131

AC:

AN:

765730

Other (OTH)

AF:

0.00

AC:

AN:

40804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.82

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

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2-215361861-GTTTTT-GTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over