dbSNP rs17160149: FBN3:c.7088-58T>G (chr19-8083430-A-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.7088-58T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,597,338 control chromosomes in the GnomAD database, including 80,046 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 0.33 ( 8617 hom., cov: 31)

Exomes 𝑓: 0.31 ( 71429 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

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:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN3	NM_032447.5	MANE Select	c.7088-58T>G		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.7088-58T>G		intron	N/A	NP_001308360.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBN3	ENST00000600128.6	TSL:1 MANE Select	c.7088-58T>G	intron	N/A	ENSP00000470498.1
FBN3	ENST00000270509.6	TSL:1	c.7088-58T>G	intron	N/A	ENSP00000270509.2
FBN3	ENST00000601739.5	TSL:1	c.7088-58T>G	intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50419

AN:

151936

Hom.:

8610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.349

GnomAD4 exome

AF:

0.311

AC:

449043

AN:

1445282

Hom.:

71429

AF XY:

0.306

AC XY:

220279

AN XY:

719094

show subpopulations

African (AFR)

AF:

0.373

AC:

12455

AN:

33362

American (AMR)

AF:

0.455

AC:

20256

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

6210

AN:

25894

East Asian (EAS)

AF:

0.273

AC:

10829

AN:

39596

South Asian (SAS)

AF:

0.199

AC:

17137

AN:

85940

European-Finnish (FIN)

AF:

0.319

AC:

15509

AN:

48542

Middle Eastern (MID)

AF:

0.246

AC:

1412

AN:

5734

European-Non Finnish (NFE)

AF:

0.315

AC:

347070

AN:

1101698

Other (OTH)

AF:

0.303

AC:

18165

AN:

59958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

14653

29306

43960

58613

73266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11448

22896

34344

45792

57240

<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:

0.332

AC:

50453

AN:

152056

Hom.:

8617

Cov.:

AF XY:

0.330

AC XY:

24566

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.366

AC:

15165

AN:

41458

American (AMR)

AF:

0.429

AC:

6561

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

831

AN:

3472

East Asian (EAS)

AF:

0.247

AC:

1276

AN:

5162

South Asian (SAS)

AF:

0.190

AC:

918

AN:

4822

European-Finnish (FIN)

AF:

0.321

AC:

3395

AN:

10582

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21318

AN:

67960

Other (OTH)

AF:

0.345

AC:

730

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.314

Hom.:

32459

Bravo

AF:

0.344

Asia WGS

AF:

0.253

AC:

877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.2

(source)

DANN

Benign

0.59

PhyloP100

-0.030

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