rs17261710

Positions:

• chr19-8071514-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.8088+534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,192 control chromosomes in the GnomAD database, including 1,458 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 0.13 (1458 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN3	NM_032447.5	c.8088+534A>G		intron_variant		ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.8088+534A>G		intron_variant		1	NM_032447.5
FBN3	ENST00000270509.6	c.8088+534A>G		intron_variant		1
FBN3	ENST00000601739.5	c.8088+534A>G		intron_variant		1
FBN3	ENST00000651877.1	c.8214+534A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19346 AN: 152074 Hom.: 1454 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.127 AC: 19355 AN: 152192 Hom.: 1458 Cov.: 32 AF XY: 0.129 AC XY: 9580 AN XY: 74418

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.124

Alfa AF: 0.162 Hom.: 3382

Bravo AF: 0.119

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.84

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: rs17261710; hg19: chr19-8136398;