rs12984611

Positions:

• chr19-8091376-C-T

Variant summary

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

The ENST00000600128.6(FBN3):​c.6031+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,524,050 control chromosomes in the GnomAD database, including 38,400 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 (3115 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35285 hom.)
• Consequence: FBN3 ENST00000600128.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.59

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.6031+89G>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.6031+89G>A		intron_variant		1	NM_032447.5	ENSP00000470498
FBN3	ENST00000270509.6	c.6031+89G>A		intron_variant		1		ENSP00000270509
FBN3	ENST00000601739.5	c.6031+89G>A		intron_variant		1		ENSP00000472324
FBN3	ENST00000651877.1	c.6157+89G>A		intron_variant				ENSP00000498507	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30115 AN: 152096 Hom.: 3103 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.224 AC: 307482 AN: 1371836 Hom.: 35285 AF XY: 0.224 AC XY: 152241 AN XY: 678960

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.198 AC: 30157 AN: 152214 Hom.: 3115 Cov.: 32 AF XY: 0.196 AC XY: 14609 AN XY: 74430

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.207

Alfa AF: 0.211 Hom.: 433

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.010
DANN	Benign	0.60

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: rs12984611; hg19: chr19-8156260;