dbSNP rs12984611: FBN3:c.6031+89G>A (chr19-8091376-C-T) – 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.6031+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,524,050 control chromosomes in the GnomAD database, including 38,400 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 0.20 ( 3115 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35285 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.59

Publications

6 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 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.6031+89G>A		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.6031+89G>A		intron	N/A	NP_001308360.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBN3	ENST00000600128.6	TSL:1 MANE Select	c.6031+89G>A	intron	N/A	ENSP00000470498.1
FBN3	ENST00000270509.6	TSL:1	c.6031+89G>A	intron	N/A	ENSP00000270509.2
FBN3	ENST00000601739.5	TSL:1	c.6031+89G>A	intron	N/A	ENSP00000472324.1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30115

AN:

152096

Hom.:

3103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.224

AC:

307482

AN:

1371836

Hom.:

35285

AF XY:

0.224

AC XY:

152241

AN XY:

678960

show subpopulations

African (AFR)

AF:

0.142

AC:

4413

AN:

31104

American (AMR)

AF:

0.196

AC:

7317

AN:

37316

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

5840

AN:

21862

East Asian (EAS)

AF:

0.140

AC:

5474

AN:

39110

South Asian (SAS)

AF:

0.209

AC:

15706

AN:

75194

European-Finnish (FIN)

AF:

0.203

AC:

10167

AN:

50198

Middle Eastern (MID)

AF:

0.242

AC:

1309

AN:

5410

European-Non Finnish (NFE)

AF:

0.232

AC:

244622

AN:

1054694

Other (OTH)

AF:

0.222

AC:

12634

AN:

56948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

11501

23002

34504

46005

57506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8408

16816

25224

33632

42040

<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:

0.198

AC:

30157

AN:

152214

Hom.:

3115

Cov.:

AF XY:

0.196

AC XY:

14609

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.147

AC:

6092

AN:

41554

American (AMR)

AF:

0.201

AC:

3070

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

868

AN:

3470

East Asian (EAS)

AF:

0.135

AC:

697

AN:

5178

South Asian (SAS)

AF:

0.195

AC:

941

AN:

4820

European-Finnish (FIN)

AF:

0.196

AC:

2072

AN:

10598

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.231

AC:

15716

AN:

68000

Other (OTH)

AF:

0.207

AC:

436

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1235

2470

3705

4940

6175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.211

Hom.:

433

Bravo

AF:

0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.010

(source)

DANN

Benign

0.60

PhyloP100

-4.6

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