chr19-8078281-C-T

Position:

• chr19-8078281-C-T

Variant summary

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

The NM_032447.5(FBN3):​c.7453+2722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,014 control chromosomes in the GnomAD database, including 31,376 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 0.62 (31376 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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 = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.7453+2722G>A		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.7453+2722G>A		intron_variant		1	NM_032447.5	ENSP00000470498

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94895 AN: 151896 Hom.: 31331 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.625 AC: 95004 AN: 152014 Hom.: 31376 Cov.: 32 AF XY: 0.621 AC XY: 46138 AN XY: 74300

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.600

Alfa AF: 0.545 Hom.: 46388

Bravo AF: 0.637

Asia WGS AF: 0.429 AC: 1494 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	1.9
DANN	Benign	0.81

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: rs3745393; hg19: chr19-8143165;