19-8070286-A-G

Position:

• chr19-8070286-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.8088+1762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,096 control chromosomes in the GnomAD database, including 9,686 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 0.28 (9686 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN3	NM_032447.5	c.8088+1762T>C		intron_variant		ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.8088+1762T>C		intron_variant		1	NM_032447.5
FBN3	ENST00000270509.6	c.8088+1762T>C		intron_variant		1
FBN3	ENST00000601739.5	c.8088+1762T>C		intron_variant		1
FBN3	ENST00000651877.1	c.8214+1762T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42696 AN: 151978 Hom.: 9648 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.281 AC: 42788 AN: 152096 Hom.: 9686 Cov.: 32 AF XY: 0.286 AC XY: 21272 AN XY: 74370

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.256

Alfa AF: 0.175 Hom.: 964

Bravo AF: 0.302

Asia WGS AF: 0.353 AC: 1226 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	1.1
DANN	Benign	0.66

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: rs10424096; hg19: chr19-8135170;