19-8093848-T-C

Position:

• chr19-8093848-T-C

Variant summary

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

The NM_032447.5(FBN3):​c.5905+598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,206 control chromosomes in the GnomAD database, including 235 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 0.023 (235 hom., cov: 33)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN3	NM_032447.5	c.5905+598A>G		intron_variant		ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.5905+598A>G		intron_variant		1	NM_032447.5
FBN3	ENST00000270509.6	c.5905+598A>G		intron_variant		1
FBN3	ENST00000601739.5	c.5905+598A>G		intron_variant		1
FBN3	ENST00000651877.1	c.6031+598A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3459 AN: 152088 Hom.: 232 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0228 AC: 3470 AN: 152206 Hom.: 235 Cov.: 33 AF XY: 0.0290 AC XY: 2161 AN XY: 74428

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.0663

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.00995 Hom.: 8

Bravo AF: 0.0228

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.73

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: rs17160153; hg19: chr19-8158732;