rs73503752

Variant names:

• chr19-8084117-C-T
• rs73503752
• NM_032447.5:c.7088-745G>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.7088-745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,782 control chromosomes in the GnomAD database, including 3,985 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 0.23 (3985 hom., cov: 30)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 2 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 = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.7088-745G>A		intron_variant	Intron 56 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.7088-745G>A		intron_variant	Intron 56 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.7088-745G>A		intron_variant	Intron 55 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.7088-745G>A		intron_variant	Intron 56 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.7214-745G>A		intron_variant	Intron 56 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34320 AN: 151662 Hom.: 3983 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.226 AC: 34345 AN: 151782 Hom.: 3985 Cov.: 30 AF XY: 0.226 AC XY: 16778 AN XY: 74164

African (AFR) AF: 0.243 AC: 10077 AN: 41418

American (AMR) AF: 0.156 AC: 2374 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3468

East Asian (EAS) AF: 0.119 AC: 608 AN: 5102

South Asian (SAS) AF: 0.156 AC: 749 AN: 4808

European-Finnish (FIN) AF: 0.271 AC: 2856 AN: 10550

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16308 AN: 67874

Other (OTH) AF: 0.203 AC: 427 AN: 2106

Alfa AF: 0.239 Hom.: 1668

Bravo AF: 0.216

Asia WGS AF: 0.145 AC: 508 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	2.8
DANN	Benign	0.75
PhyloP100		0.39
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: rs73503752; hg19: chr19-8149001;