rs2086149

Positions:

• chr19-8112736-C-T

Variant summary

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

The NM_032447.5(FBN3):​c.3839-637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,116 control chromosomes in the GnomAD database, including 10,168 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 0.36 (10168 hom., cov: 33)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.3839-637G>A		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.3839-637G>A		intron_variant		1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6	c.3839-637G>A		intron_variant		1		ENSP00000270509
FBN3	ENST00000601739.5	c.3839-637G>A		intron_variant		1		ENSP00000472324
FBN3	ENST00000651877.1	c.3965-637G>A		intron_variant				ENSP00000498507	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53968 AN: 151998 Hom.: 10152 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 54021 AN: 152116 Hom.: 10168 Cov.: 33 AF XY: 0.366 AC XY: 27197 AN XY: 74354

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.315

Alfa AF: 0.295 Hom.: 9170

Bravo AF: 0.349

Asia WGS AF: 0.462 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.86

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: rs2086149; hg19: chr19-8177620;