rs8103000

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032447.5(FBN3):​c.6755-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,565,376 control chromosomes in the GnomAD database, including 1 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 0.0011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.610
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBN3NM_032447.5 linkuse as main transcriptc.6755-30C>T intron_variant ENST00000600128.6 NP_115823.3 Q75N90A8KAY2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBN3ENST00000600128.6 linkuse as main transcriptc.6755-30C>T intron_variant 1 NM_032447.5 ENSP00000470498.1 Q75N90
FBN3ENST00000270509.6 linkuse as main transcriptc.6755-30C>T intron_variant 1 ENSP00000270509.2 Q75N90
FBN3ENST00000601739.5 linkuse as main transcriptc.6755-30C>T intron_variant 1 ENSP00000472324.1 Q75N90
FBN3ENST00000651877.1 linkuse as main transcriptc.6881-30C>T intron_variant ENSP00000498507.1 A0A494C0D8

Frequencies

GnomAD3 genomes
AF:
0.00113
AC:
171
AN:
151904
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00380
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.000233
AC:
51
AN:
218562
Hom.:
1
AF XY:
0.000204
AC XY:
24
AN XY:
117890
show subpopulations
Gnomad AFR exome
AF:
0.00282
Gnomad AMR exome
AF:
0.0000968
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000120
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000305
Gnomad OTH exome
AF:
0.000194
GnomAD4 exome
AF:
0.000125
AC:
177
AN:
1413358
Hom.:
1
Cov.:
30
AF XY:
0.000129
AC XY:
90
AN XY:
697536
show subpopulations
Gnomad4 AFR exome
AF:
0.00426
Gnomad4 AMR exome
AF:
0.000143
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000621
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000166
Gnomad4 OTH exome
AF:
0.000172
GnomAD4 genome
AF:
0.00112
AC:
171
AN:
152018
Hom.:
0
Cov.:
31
AF XY:
0.000969
AC XY:
72
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00379
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.0000468
Hom.:
641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
2.2
DANN
Benign
0.78

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.

Other links and lift over

dbSNP: rs8103000; hg19: chr19-8151239; API