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

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=-1.0).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.7213+89C>G		intron_variant	Intron 57 of 63	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.7213+89C>G	intron_variant	Intron 57 of 63	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.7213+89C>G	intron_variant	Intron 56 of 62	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.7213+89C>G	intron_variant	Intron 57 of 63	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.7339+89C>G	intron_variant	Intron 57 of 63			ENSP00000498507.1	A0A494C0D8

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

Gnomad4 AFR exome

AF:

0.434

AC:

13585

AN:

31308

Gnomad4 AMR exome

AF:

0.456

AC:

19666

AN:

43092

Gnomad4 ASJ exome

AF:

0.240

AC:

5899

AN:

24536

Gnomad4 EAS exome

AF:

0.274

AC:

10619

AN:

38786

Gnomad4 SAS exome

AF:

0.199

AC:

16419

AN:

82498

Gnomad4 FIN exome

AF:

0.319

AC:

14763

AN:

46220

Gnomad4 NFE exome

AF:

0.315

AC:

321369

AN:

1018760

Gnomad4 Remaining exome

AF:

0.308

AC:

17380

AN:

56382

Heterozygous variant carriers

13869

27738

41608

55477

69346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.422

AC:

0.422177

AN:

0.422177

Gnomad4 AMR

AF:

0.437

AC:

0.436886

AN:

0.436886

Gnomad4 ASJ

AF:

0.239

AC:

0.239331

AN:

0.239331

Gnomad4 EAS

AF:

0.246

AC:

0.246016

AN:

0.246016

Gnomad4 SAS

AF:

0.190

AC:

0.189627

AN:

0.189627

Gnomad4 FIN

AF:

0.321

AC:

0.32084

AN:

0.32084

Gnomad4 NFE

AF:

0.314

AC:

0.314214

AN:

0.314214

Gnomad4 OTH

AF:

0.364

AC:

0.363507

AN:

0.363507

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.24

DANN

Benign

0.62

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over