Genetic Variant FBN3:c.7087+106_7087+107insCTGTGTGT (chr19-8085256-C-CACACACAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032447.5(FBN3):c.7087+106_7087+107insCTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 868,432 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 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

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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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.7087+106_7087+107insCTGTGTGT		intron_variant	Intron 56 of 63	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.7087+106_7087+107insCTGTGTGT	intron_variant	Intron 56 of 63	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.7087+106_7087+107insCTGTGTGT	intron_variant	Intron 55 of 62	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.7087+106_7087+107insCTGTGTGT	intron_variant	Intron 56 of 63	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.7213+106_7213+107insCTGTGTGT	intron_variant	Intron 56 of 63			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.000222

AC:

AN:

148848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000645

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

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:

0.0000747

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000208

AC:

AN:

719472

Hom.:

AF XY:

0.0000133

AC XY:

AN XY:

375680

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000121

AC:

AN:

16472

American (AMR)

AF:

0.0000490

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:

0.0000221

AC:

AN:

497580

Other (OTH)

AF:

0.0000282

AC:

AN:

35450

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000286097), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.372

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000222

AC:

AN:

148960

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

72702

show subpopulations

African (AFR)

AF:

0.000643

AC:

AN:

40442

American (AMR)

AF:

0.000134

AC:

AN:

14876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

4984

South Asian (SAS)

AF:

0.00

AC:

AN:

4676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000747

AC:

AN:

66960

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over