rs2303169

Positions:

• chr19-8081230-T-C

Variant summary

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

The NM_032447.5(FBN3):​c.7337-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,475,976 control chromosomes in the GnomAD database, including 228,925 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 0.62 (30194 hom., cov: 31)
  • Exomes 𝑓: 0.54 (198731 hom.)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.7337-111A>G		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.7337-111A>G		intron_variant		1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.7337-111A>G		intron_variant		1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.7337-111A>G		intron_variant		1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.7463-111A>G		intron_variant				ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93514 AN: 151782 Hom.: 30153 Cov.: 31

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.542 AC: 718074 AN: 1324076 Hom.: 198731 Cov.: 19 AF XY: 0.537 AC XY: 353295 AN XY: 658490

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.616 AC: 93616 AN: 151900 Hom.: 30194 Cov.: 31 AF XY: 0.613 AC XY: 45500 AN XY: 74244

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.594

Alfa AF: 0.602 Hom.: 3515

Bravo AF: 0.625

Asia WGS AF: 0.438 AC: 1524 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	5.9
DANN	Benign	0.62

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: rs2303169; hg19: chr19-8146114; COSMIC: COSV54459138; COSMIC: COSV54459138;