rs3813780

Variant names:

• chr19-8096726-C-T
• rs3813780
• NM_032447.5:c.5413+155G>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.5413+155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,076 control chromosomes in the GnomAD database, including 3,086 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 0.20 (3086 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.5413+155G>A		intron_variant	Intron 43 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.5413+155G>A		intron_variant	Intron 43 of 63	1	NM_032447.5	ENSP00000470498.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29993 AN: 151958 Hom.: 3078 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.197 AC: 30026 AN: 152076 Hom.: 3086 Cov.: 32 AF XY: 0.196 AC XY: 14589 AN XY: 74346

African (AFR) AF: 0.146 AC: 6066 AN: 41486

American (AMR) AF: 0.199 AC: 3037 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3468

East Asian (EAS) AF: 0.184 AC: 953 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10596

Middle Eastern (MID) AF: 0.260 AC: 75 AN: 288

European-Non Finnish (NFE) AF: 0.224 AC: 15256 AN: 67958

Other (OTH) AF: 0.211 AC: 445 AN: 2108

Alfa AF: 0.203 Hom.: 404

Bravo AF: 0.196

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.31
PhyloP100		-3.5
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: rs3813780; hg19: chr19-8161610; COSMIC: COSV107212437;