Genetic Variant FBN3:c.6755-30C>G (chr19-8086355-G-C) – 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.6755-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,563,828 control chromosomes in the GnomAD database, including 68,834 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 0.31 ( 7489 hom., cov: 31)

Exomes 𝑓: 0.29 ( 61345 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.610

Publications

9 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

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.6755-30C>G		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.6755-30C>G		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.6755-30C>G	intron	N/A	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6	TSL:1	c.6755-30C>G	intron	N/A	ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5	TSL:1	c.6755-30C>G	intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46940

AN:

151854

Hom.:

7469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.308

GnomAD2 exomes

AF:

0.317

AC:

69195

AN:

218562

AF XY:

0.308

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.291

AC:

410609

AN:

1411860

Hom.:

61345

Cov.:

AF XY:

0.289

AC XY:

201537

AN XY:

696790

show subpopulations

African (AFR)

AF:

0.327

AC:

10489

AN:

32100

American (AMR)

AF:

0.450

AC:

18847

AN:

41914

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

5561

AN:

24048

East Asian (EAS)

AF:

0.398

AC:

14913

AN:

37424

South Asian (SAS)

AF:

0.283

AC:

22745

AN:

80394

European-Finnish (FIN)

AF:

0.283

AC:

14659

AN:

51800

Middle Eastern (MID)

AF:

0.225

AC:

1253

AN:

5562

European-Non Finnish (NFE)

AF:

0.282

AC:

305091

AN:

1080390

Other (OTH)

AF:

0.293

AC:

17051

AN:

58228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13456

26912

40368

53824

67280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10584

21168

31752

42336

52920

<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:

0.309

AC:

46990

AN:

151968

Hom.:

7489

Cov.:

AF XY:

0.309

AC XY:

22974

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.331

AC:

13725

AN:

41442

American (AMR)

AF:

0.390

AC:

5958

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

793

AN:

3470

East Asian (EAS)

AF:

0.395

AC:

2037

AN:

5162

South Asian (SAS)

AF:

0.276

AC:

1329

AN:

4814

European-Finnish (FIN)

AF:

0.290

AC:

3059

AN:

10566

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.284

AC:

19259

AN:

67922

Other (OTH)

AF:

0.305

AC:

643

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1669

3339

5008

6678

8347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.204

Hom.:

641

Bravo

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.69

(source)

DANN

Benign

0.51

PhyloP100

-0.61

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over