chr19-8083430-A-C

Position:

• chr19-8083430-A-C

Variant summary

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

The NM_032447.5(FBN3):​c.7088-58T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,597,338 control chromosomes in the GnomAD database, including 80,046 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 0.33 (8617 hom., cov: 31)
  • Exomes 𝑓: 0.31 (71429 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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 (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.7088-58T>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.7088-58T>G		intron_variant		1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.7088-58T>G		intron_variant		1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.7088-58T>G		intron_variant		1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.7214-58T>G		intron_variant				ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50419 AN: 151936 Hom.: 8610 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.311 AC: 449043 AN: 1445282 Hom.: 71429 AF XY: 0.306 AC XY: 220279 AN XY: 719094

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.332 AC: 50453 AN: 152056 Hom.: 8617 Cov.: 31 AF XY: 0.330 AC XY: 24566 AN XY: 74346

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.345

Alfa AF: 0.309 Hom.: 14809

Bravo AF: 0.344

Asia WGS AF: 0.253 AC: 877 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	5.2
DANN	Benign	0.59

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: rs17160149; hg19: chr19-8148314; COSMIC: COSV54466807; COSMIC: COSV54466807;