19-8086355-G-C

Position:

• chr19-8086355-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.6755-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,563,828 control chromosomes in the GnomAD database, including 68,834 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 0.31 (7489 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61345 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.6755-30C>G		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.6755-30C>G		intron_variant		1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.6755-30C>G		intron_variant		1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.6755-30C>G		intron_variant		1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.6881-30C>G		intron_variant				ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46940 AN: 151854 Hom.: 7469 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.308

GnomAD3 exomes AF: 0.317 AC: 69195 AN: 218562 Hom.: 11613 AF XY: 0.308 AC XY: 36266 AN XY: 117890

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.284

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.291 AC: 410609 AN: 1411860 Hom.: 61345 Cov.: 30 AF XY: 0.289 AC XY: 201537 AN XY: 696790

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.309 AC: 46990 AN: 151968 Hom.: 7489 Cov.: 31 AF XY: 0.309 AC XY: 22974 AN XY: 74268

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.305

Alfa AF: 0.204 Hom.: 641

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.69
DANN	Benign	0.51

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: rs8103000; hg19: chr19-8151239;