rs17160147

chr19-8083158-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-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/exons	MANE	UniProt
FBN3	NM_032447.5	c.7213+89C>G		intron_variant		ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.7213+89C>G		intron_variant		1	NM_032447.5
FBN3	ENST00000270509.6	c.7213+89C>G		intron_variant		1
FBN3	ENST00000601739.5	c.7213+89C>G		intron_variant		1
FBN3	ENST00000651877.1	c.7339+89C>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52921 AN: 151910 Hom.: 9651 Cov.: 31

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

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.348 AC: 52966 AN: 152030 Hom.: 9659 Cov.: 31 AF XY: 0.347 AC XY: 25753 AN XY: 74292

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.364

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

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

Other links and lift over

dbSNP: rs17160147; hg19: chr19-8148042;