dbSNP rs12981294: FBN3:c.6031+128T>C (chr19-8091337-A-G) – 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+128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,287,608 control chromosomes in the GnomAD database, including 32,124 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 ( 3113 hom., cov: 32)

Exomes 𝑓: 0.22 ( 29011 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0130

Publications

3 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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.6031+128T>C		intron_variant	Intron 48 of 63	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.6031+128T>C	intron_variant	Intron 48 of 63	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.6031+128T>C	intron_variant	Intron 47 of 62	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.6031+128T>C	intron_variant	Intron 48 of 63	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.6157+128T>C	intron_variant	Intron 48 of 63			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30114

AN:

151214

Hom.:

3101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.224

AC:

254291

AN:

1136280

Hom.:

29011

AF XY:

0.224

AC XY:

126979

AN XY:

567724

show subpopulations

African (AFR)

AF:

0.145

AC:

3671

AN:

25364

American (AMR)

AF:

0.195

AC:

5949

AN:

30492

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

5044

AN:

18812

East Asian (EAS)

AF:

0.140

AC:

5303

AN:

37858

South Asian (SAS)

AF:

0.207

AC:

13668

AN:

65916

European-Finnish (FIN)

AF:

0.201

AC:

8944

AN:

44468

Middle Eastern (MID)

AF:

0.243

AC:

1180

AN:

4854

European-Non Finnish (NFE)

AF:

0.232

AC:

199742

AN:

859762

Other (OTH)

AF:

0.221

AC:

10790

AN:

48754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9410

18819

28229

37638

47048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.199

AC:

30156

AN:

151328

Hom.:

3113

Cov.:

AF XY:

0.197

AC XY:

14597

AN XY:

73978

show subpopulations

African (AFR)

AF:

0.150

AC:

6090

AN:

40716

American (AMR)

AF:

0.202

AC:

3072

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

868

AN:

3472

East Asian (EAS)

AF:

0.134

AC:

696

AN:

5184

South Asian (SAS)

AF:

0.195

AC:

940

AN:

4824

European-Finnish (FIN)

AF:

0.195

AC:

2067

AN:

10606

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15720

AN:

67992

Other (OTH)

AF:

0.208

AC:

437

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1272

2545

3817

5090

6362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.222

Hom.:

5671

Bravo

AF:

0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.7

(source)

DANN

Benign

0.68

PhyloP100

0.013

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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rs12981294

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over