Genetic Variant FBN3:c.7213+89C>G (chr19-8083158-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.7213+89C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,498,682 control chromosomes in the GnomAD database, including 77,500 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 0.35 ( 9659 hom., cov: 31)

Exomes 𝑓: 0.31 ( 67841 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

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=-1.0).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 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.7213+89C>G		intron	N/A	NP_115823.3
	FBN3	NM_001321431.2		c.7213+89C>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.7213+89C>G	intron	N/A	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6	TSL:1	c.7213+89C>G	intron	N/A	ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5	TSL:1	c.7213+89C>G	intron	N/A	ENSP00000472324.1	Q75N90

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52921

AN:

151910

Hom.:

9651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.367

GnomAD4 exome

AF:

0.313

AC:

420982

AN:

1346652

Hom.:

67841

AF XY:

0.308

AC XY:

206625

AN XY:

671294

show subpopulations

African (AFR)

AF:

0.434

AC:

13585

AN:

31308

American (AMR)

AF:

0.456

AC:

19666

AN:

43092

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

5899

AN:

24536

East Asian (EAS)

AF:

0.274

AC:

10619

AN:

38786

South Asian (SAS)

AF:

0.199

AC:

16419

AN:

82498

European-Finnish (FIN)

AF:

0.319

AC:

14763

AN:

46220

Middle Eastern (MID)

AF:

0.253

AC:

1282

AN:

5070

European-Non Finnish (NFE)

AF:

0.315

AC:

321369

AN:

1018760

Other (OTH)

AF:

0.308

AC:

17380

AN:

56382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13869

27738

41608

55477

69346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10454

20908

31362

41816

52270

<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:

0.348

AC:

52966

AN:

152030

Hom.:

9659

Cov.:

AF XY:

0.347

AC XY:

25753

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.422

AC:

17506

AN:

41466

American (AMR)

AF:

0.437

AC:

6673

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

830

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1266

AN:

5146

South Asian (SAS)

AF:

0.190

AC:

914

AN:

4820

European-Finnish (FIN)

AF:

0.321

AC:

3390

AN:

10566

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21359

AN:

67976

Other (OTH)

AF:

0.364

AC:

767

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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

506

1012

1518

2024

2530

<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:

0.329

Hom.:

1068

Bravo

AF:

0.364

Asia WGS

AF:

0.263

AC:

912

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.24

(source)

DANN

Benign

0.62

PhyloP100

-1.6

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