rs7252584

Positions:

• chr19-8142357-C-G

Variant summary

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

The NM_032447.5(FBN3):​c.542-220G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,100 control chromosomes in the GnomAD database, including 1,513 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 0.14 (1513 hom., cov: 31)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.542-220G>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.542-220G>C		intron_variant		1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.542-220G>C		intron_variant		1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.542-220G>C		intron_variant		1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.542-220G>C		intron_variant				ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20979 AN: 151980 Hom.: 1511 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.138 AC: 20987 AN: 152100 Hom.: 1513 Cov.: 31 AF XY: 0.141 AC XY: 10502 AN XY: 74358

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.152

Alfa AF: 0.133 Hom.: 177

Bravo AF: 0.137

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.0
DANN	Benign	0.77

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: rs7252584; hg19: chr19-8207241;