rs17202517

Positions:

• chr19-8083417-G-A
• chr19-8083417-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):​c.7088-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,603,190 control chromosomes in the GnomAD database, including 39,622 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 0.17 (2771 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36851 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN3	NM_032447.5	c.7088-45C>T		intron_variant		ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.7088-45C>T		intron_variant		1	NM_032447.5
FBN3	ENST00000270509.6	c.7088-45C>T		intron_variant		1
FBN3	ENST00000601739.5	c.7088-45C>T		intron_variant		1
FBN3	ENST00000651877.1	c.7214-45C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25802 AN: 152024 Hom.: 2768 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.188 AC: 46367 AN: 247026 Hom.: 5015 AF XY: 0.192 AC XY: 25639 AN XY: 133702

Gnomad AFR exome AF: 0.0414

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.218 AC: 315838 AN: 1451048 Hom.: 36851 Cov.: 32 AF XY: 0.217 AC XY: 156446 AN XY: 721958

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.170 AC: 25805 AN: 152142 Hom.: 2771 Cov.: 32 AF XY: 0.170 AC XY: 12665 AN XY: 74366

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.155

Alfa AF: 0.212 Hom.: 4953

Bravo AF: 0.151

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs17202517; hg19: chr19-8148301; COSMIC: COSV54459161; COSMIC: COSV54459161;