Genetic Variant FBN3:c.*383G>C (chr19-8065536-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032447.5(FBN3):c.*383G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 216,934 control chromosomes in the GnomAD database, including 3,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2002 hom., cov: 33)

Exomes 𝑓: 0.17 ( 1163 hom. )

Consequence

FBN3
NM_032447.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.798

Publications

7 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.*383G>C		3_prime_UTR_variant	Exon 64 of 64	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.*383G>C	3_prime_UTR_variant	Exon 64 of 64	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.*383G>C	3_prime_UTR_variant	Exon 63 of 63	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.*383G>C	3_prime_UTR_variant	Exon 64 of 64	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.*383G>C	3_prime_UTR_variant	Exon 64 of 64			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21660

AN:

152118

Hom.:

2007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.171

AC:

11040

AN:

64698

Hom.:

1163

Cov.:

AF XY:

0.170

AC XY:

5514

AN XY:

32386

show subpopulations

African (AFR)

AF:

0.0341

AC:

AN:

2522

American (AMR)

AF:

0.123

AC:

254

AN:

2062

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

372

AN:

2604

East Asian (EAS)

AF:

0.394

AC:

1862

AN:

4730

South Asian (SAS)

AF:

0.173

AC:

144

AN:

832

European-Finnish (FIN)

AF:

0.184

AC:

719

AN:

3898

Middle Eastern (MID)

AF:

0.182

AC:

AN:

384

European-Non Finnish (NFE)

AF:

0.158

AC:

6810

AN:

43080

Other (OTH)

AF:

0.158

AC:

723

AN:

4586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

412

824

1236

1648

2060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.142

AC:

21655

AN:

152236

Hom.:

2002

Cov.:

AF XY:

0.146

AC XY:

10839

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0425

AC:

1765

AN:

41576

American (AMR)

AF:

0.125

AC:

1911

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

593

AN:

3468

East Asian (EAS)

AF:

0.426

AC:

2199

AN:

5168

South Asian (SAS)

AF:

0.191

AC:

921

AN:

4834

European-Finnish (FIN)

AF:

0.212

AC:

2245

AN:

10590

Middle Eastern (MID)

AF:

0.179

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.170

AC:

11545

AN:

67988

Other (OTH)

AF:

0.137

AC:

289

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

950

1899

2849

3798

4748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.0733

Hom.:

102

Bravo

AF:

0.134

Asia WGS

AF:

0.241

AC:

836

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.6

(source)

DANN

Benign

0.67

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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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