Genetic Variant NM_212482.4:c.7362+105_7362+107dupAAA (chr2-215361861-G-GTTT) – 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+105_7362+107dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000971 in 1,132,594 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: 𝑓 0.000034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000061 ( 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 afr. gnomad4_exome allele frequency = 0.00000609 (6/985784) while in subpopulation AFR AF= 0.000227 (5/22016). AF 95% confidence interval is 0.0000891. There are 0 homozygotes in gnomad4_exome. There are 4 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN1	NM_212482.4 link	c.7362+105_7362+107dupAAA		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+108insAAA		intron_variant	Intron 45 of 45	1	NM_212482.4	ENSP00000346839.4		P02751-15

Frequencies

GnomAD3 genomes

AF:

0.0000341

AC:

AN:

146810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000609

AC:

AN:

985784

Hom.:

Cov.:

AF XY:

0.00000821

AC XY:

AN XY:

487000

show subpopulations

Gnomad4 AFR exome

AF:

0.000227

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000245

GnomAD4 genome

AF:

0.0000341

AC:

AN:

146810

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

71468

show subpopulations

Gnomad4 AFR

AF:

0.000125

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

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