19-8121635-A-G

Position:

• chr19-8121635-A-G

Variant summary

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

The NM_032447.5(FBN3):​c.3083-249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,754 control chromosomes in the GnomAD database, including 34,982 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 0.67 (34982 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.3083-249T>C		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.3083-249T>C		intron_variant		1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6	c.3083-249T>C		intron_variant		1		ENSP00000270509
FBN3	ENST00000601739.5	c.3083-249T>C		intron_variant		1		ENSP00000472324
FBN3	ENST00000651877.1	c.3209-249T>C		intron_variant				ENSP00000498507	P1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101074 AN: 151636 Hom.: 34917 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.667 AC: 101204 AN: 151754 Hom.: 34982 Cov.: 32 AF XY: 0.673 AC XY: 49910 AN XY: 74122

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.630

Alfa AF: 0.562 Hom.: 48032

Bravo AF: 0.677

Asia WGS AF: 0.750 AC: 2608 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	0.35
DANN	Benign	0.28

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: rs4527136; hg19: chr19-8186519;