rs8111335

Variant names:

• chr19-8111477-G-A
• rs8111335
• NM_032447.5:c.4084+171C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):​c.4084+171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,034 control chromosomes in the GnomAD database, including 1,751 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 0.14 (1751 hom., cov: 32)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.4084+171C>T		intron_variant	Intron 32 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.4084+171C>T		intron_variant	Intron 32 of 63	1	NM_032447.5	ENSP00000470498.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21067 AN: 151916 Hom.: 1748 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0974

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.139 AC: 21098 AN: 152034 Hom.: 1751 Cov.: 32 AF XY: 0.140 AC XY: 10411 AN XY: 74324

African (AFR) AF: 0.235 AC: 9727 AN: 41448

American (AMR) AF: 0.0971 AC: 1484 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5164

South Asian (SAS) AF: 0.133 AC: 639 AN: 4808

European-Finnish (FIN) AF: 0.135 AC: 1431 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6965 AN: 67948

Other (OTH) AF: 0.128 AC: 270 AN: 2106

Alfa AF: 0.121 Hom.: 159

Bravo AF: 0.141

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.76
PhyloP100		-1.2
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: rs8111335; hg19: chr19-8176361;