chr19-8103456-T-A

Position:

• chr19-8103456-T-A

Variant summary

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

The NM_032447.5(FBN3):​c.4939+106A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,195,472 control chromosomes in the GnomAD database, including 7,673 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 0.096 (796 hom., cov: 30)
  • Exomes 𝑓: 0.11 (6877 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.4939+106A>T		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.4939+106A>T		intron_variant		1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.4939+106A>T		intron_variant		1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.4939+106A>T		intron_variant		1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.5065+106A>T		intron_variant				ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14577 AN: 151928 Hom.: 790 Cov.: 30

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.111 AC: 115743 AN: 1043426 Hom.: 6877 AF XY: 0.111 AC XY: 58320 AN XY: 526018

Gnomad4 AFR exome AF: 0.0573

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.0595

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.0960 AC: 14598 AN: 152046 Hom.: 796 Cov.: 30 AF XY: 0.0931 AC XY: 6921 AN XY: 74308

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0441 Hom.: 44

Bravo AF: 0.100

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3865464; hg19: chr19-8168340;