rs3745393

Variant names:

• chr19-8078281-C-T
• rs3745393
• NM_032447.5:c.7453+2722G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.7453+2722G>A		intron_variant	Intron 59 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.7453+2722G>A		intron_variant	Intron 59 of 63	1	NM_032447.5	ENSP00000470498.1

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

African (AFR) AF: 0.841 AC: 34886 AN: 41474

American (AMR) AF: 0.616 AC: 9393 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1859 AN: 5158

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4818

European-Finnish (FIN) AF: 0.587 AC: 6202 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37401 AN: 67958

Other (OTH) AF: 0.600 AC: 1268 AN: 2112

Alfa AF: 0.565 Hom.: 78109

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3745393; hg19: chr19-8143165;