Genetic Variant FBN3:c.7087+106_7087+107insCTGT (chr19-8085256-C-CACAG) – 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_032447.5(FBN3):c.7087+106_7087+107insCTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 148,848 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBN3
NM_032447.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.393

Publications

1 publications found

Variant links:

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

FBN3 links:

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new If you want to explore the variant's impact on the transcript NM_032447.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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_032447.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.7087+106_7087+107insCTGT		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.7087+106_7087+107insCTGT		intron	N/A	NP_001308360.1	Q75N90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBN3	ENST00000600128.6	TSL:1 MANE Select	c.7087+106_7087+107insCTGT	intron	N/A	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6	TSL:1	c.7087+106_7087+107insCTGT	intron	N/A	ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5	TSL:1	c.7087+106_7087+107insCTGT	intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

148848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000496

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

719478

Hom.:

AF XY:

0.00

AC XY:

AN XY:

375682

African (AFR)

AF:

0.00

AC:

AN:

16476

American (AMR)

AF:

0.00

AC:

AN:

20404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18916

East Asian (EAS)

AF:

0.00

AC:

AN:

31534

South Asian (SAS)

AF:

0.00

AC:

AN:

59076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

497582

Other (OTH)

AF:

0.00

AC:

AN:

35450

GnomAD4 genome

AF:

0.0000134

AC:

AN:

148848

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72576

show subpopulations

African (AFR)

AF:

0.0000496

AC:

AN:

40324

American (AMR)

AF:

0.00

AC:

AN:

14856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

4996

South Asian (SAS)

AF:

0.00

AC:

AN:

4680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66970

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over